• The Korean Journal of Physiology and Pharmacology
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• v.16 no.6
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• pp.399-404
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• 2012

We investigated inhibitory effects of extract containing quercetin-3-O-${\beta}$-D-glucuronopyranoside (ECQ) extracted from Rumex Aquaticus Herba on indomethacin-induced gastric damage in Rats. Gastritis was induced in male Sprague-Dawley rats (200~220 g) by oral administration of indomethacin at a dose of 40 mg/kg. One hour before administration of indomethacin, animals were orally pretreated with ECQ at doses of 0.3, 1, 3 or 10 mg/kg. Six hours after indomethacin administration, the rats were sacrificed and the stomach was excised and opened along the greater curvature, and the surface area of gastric lesion was measured using optical microscope. Superoxide dismutase (SOD), catalase (CAT), myeloperoxidase (MPO) activities and malondialdehyde (MDA) levels were measured by ELISA. Western blot analysis was performed to detect protein expression of SOD-2. Linear hemorrhagic mucosal lesions were observed in the stomach 6 hours after oral administration of indomethacin. Pretreatment with ECQ significantly reduced the severity of the lesions in a dose-dependent manner. It also inhibited the reductions in SOD and CAT activities and SOD expression by the indomethacin-induced gastric damage. In addition, the pretreatment with ECQ significantly suppressed the elevation of the MPO activity and the MDA levels induced by indomethacin. These results suggest that ECQ has the inhibitory effects via antioxidative action against indomethacin-induced gastritis in rats.

• Journal of Pharmaceutical Investigation
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• v.18 no.3
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• pp.133-137
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• 1988

In vitro studies were performed on the interaction of indomethacin with cholestyramine, a hypocholesterolemic substance. Cholestyramine showed a marked affinity for indomethacin among tested acidic drugs and the intensity of adsorption was dependent on pH, temperature and sodium chloride. Moreover, the combination of indomethacin with some acidic drugs that formed complexes with cholestyramine, considerably inhibited the adsorption of indomethacin on the resin.

• YAKHAK HOEJI
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• v.43 no.2
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• pp.214-220
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• 1999

Present study was aimed to examine whether indomethacin affected the production of NO in the rat paw exudate by carrageenin. Paw edema and nitrite/nitrate levels in the paw exudate were maximal after 4 h and remained elevated up to 10 h, whereas indomethacin (10 mg/kg, po) significantly inhibited the carrageenin-induced paw edema and levels of nitrate in the paw exudate. However, paw edema and nitrite/nitrite levels were increased thereafter for 10 h. Indomethacin also enhanced the expression of iNOS mRNA and protein 4 h after carrageenin infection. Indomethacin inhibited the level of $PGE_2$ in the paw exudate in a time-dependent manner. These results suggest the possibility that indomethacin may potentiate expression of iNOS and subsequently increase nitrite/nitrate level in the late phase of carrageenin-induced rat paw inflammation possibly by suppressing cycloxygenase activity.

• Journal of Pharmaceutical Investigation
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• v.12 no.3
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• pp.74-87
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• 1982

To evaluate the pharmaceutical aspects of solvent deposition method where drug is solvent deposited on the surface of excipients, a study has been made on dissolution characteristics of indomethacin solvent deposited on lactose and potato starch. In a solvent deposition system, the drug-to-excipient ratio and kind of excipient effect much on dissolution rates of indomethacin. The experimental results are as follows: 1) Lactose was shown to be superior to potato starch as excipients in indomethacin solvent deposited. 2) Total amount of indomethacin dissolved from solvent deposition systems at 30 minutes were enhanced about 5 to 23 times compared with that of pure indomethacin. 3) Increased dissotion amount of indomethacin from the solvent deposition systems were observed to be alike in the systems where the drug-to-excipient weight ratios were 1 : 5, 1 : 7 and 1 : 10.

• YAKHAK HOEJI
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• v.33 no.3
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• pp.191-202
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• 1989

Indomethacin, a non-steroidal antiinflammatory drug inducing gastric irritation, was microencapsulated using pectin-gelatin complex coacervation method. Optimum conditions for microencapsulation and dissolution characteristics of the microcapsules were studied. The optimum pH and pectin-gelatin ratio for microencapsulation were 3.8 and 1:2 respectively. As concentration of colloid solution increased, wall thickness of microcapsules were increased. The dissolution rate of Indomethacin-pectin-gelatin microcapsules prepared by 1.5% and 2% colloid solution were similar but slower than that of Indomethacin-pectin-gelatin microcapsules prepared by 1% colloid solution. The 50% release time ($T_{50%}$) of Indomethacin-pectin-gelatin microcapsules prepared by 1%, 1.5% and 2% colloid solutions were 3 min, 5 min, and 6 min respectively while that of Indomethacin powder was 50 min.

• The korean journal of orthodontics
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• v.26 no.2 s.55
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• pp.163-174
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• 1996

The purpose of this study was to examine the effects of bisphosphonate and indomethacin, blockers of bone resorption with different mechanisms, on alveolar bone remodeling. Male rats were divided into control, bisphosphonate and indomethacin groups, and then each group was divided info an experimental side and a control side according to the force application. Bisphosphonate(6.3mg/kg,$2.52x10^{-2}mol/L$) and indomethacin (9mg/kg, $2.52x10^{-2}mol/L$) were injected 6 hours and 1 hour before or 24 hours after the force application. The rats were killed 72 hours after the force application and histologic examination was perfomed. The values of serum acid phosphatase and lactate dehydrogenase were also measured in the control md experimental groups treated with bisphosphonate or indomethacin 1 hour before the force application. In the experimental side, the least number of osteoclasts was noted in the groups treated 1 hour before the force application with indomethacin or bisphosphonate, while there were no differences between the control and the groups treated with drugs 6 hours before or 24 hours after the force application. In the control side, the number of osteoclasts was not inecreased with no differences among the groups. Histologic examination revealed a severe alveolar bone resorption in the control group and the groups treated with indomethacin 6 hours before or 24 hours after the force application. Indomethacin treatment 1 hour before the force application and bisphosphonate treatment at any time significantly attenuated the bone resorption. Electron microscopically, ruffled border and clear zone of osteoclasts were observed in the control and indomethacin groups, while some osteoclasts were detached from the bone surface and exhibited dull cellular projections in the bisphosphonate groups. The bisphosphonate and indomethacin groups showed lower values of acid phosphatase and lactate dehydrogenase than the control group. The acid phosphatase value in the bisphosphonate group was lower than that in the indomethacin group, whereas there was no difference in the lactate dehydrogenase value between the groups. These results suggest that bisphosphonate reduces the activity of osteoclasts as well as the number of osteoclasts and that indomethacin reduces the number of osteoclasts without affecting the activity of osteoclasts. Bisphosphonate has a larger inhibitory effect on bone resorption md thus less limitation in the application time than indomethacin.

• Journal of Microbiology and Biotechnology
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• v.14 no.5
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• pp.996-1003
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• 2004

Nonsteroidal anti-inflammatory drugs such as indomethacin induce severe gastric mucosal damage in humans and rodents. In the present study, the in vivo protective effect of astaxanthin on indomethacin-induced gastric lesions in rats was investigated. The test groups were injected with indomethacin (25 mg/kg) after the oral administration of astaxanthin (25 mg/kg) for 1, 2, and 3 days, while the control group was treated only with indomethacin. Thiobarbituric acid reactive substances in the gastric mucosa, as an index of lipid peroxidation, increased significantly after indomethacin administration and this increase was inhibited by oral administration of astaxanthin. In addition, pretreatment with astaxanthin resulted in a significant increase of the activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-px). Histologic examination clearly revealed acute gastric mucosal lesions induced by indomethacin in the stomach of the control group, but were not observed in that of the test group. These results indicate that astaxanthin activates SOD, catalase, and GSH-px, and removes the lipid peroxides and free radicals induced by indomethacin. It is evident that astaxanthin acts as a free radical quencher and antioxidant, and is an effective molecule in the remedy of gastric mucosal lesions.

• Journal of Pharmaceutical Investigation
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• v.25 no.2
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• pp.129-136
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• 1995

In order to reduce the systemic side effects and the gastrointestinal irritation of indomethacin following its oral administration, the drug was formulated as a transdermal gel using poloxamer 407. In vitro diffusion cells fitted with excised rat skins were used to evaluate the effects of formulation variables on skin permeation of indomethacin from poloxamer gels. The formulation variables were the concentrations of indomethacin, poloxamer 407 and ethanol, and the gel pH. The increase of the drug amount in the gel from 0.5% to 2.0% induced a direct but nonlinear increase in the skin permeation rate of indomethacin. The increase of poloxamer concentration from 17.5% to 25% in the gel resulted in a decrease of skin permeation rate of indomethacin, which was due to a reduction in the amount of free drug molecules available for permeation through skin by entrapping more drug molecules within the micelles formed by poloxamer. The increase of ethanol concentration from 10% to 20% in the gel resulted in a linear increase of permeation rate of indomethacin through skin, possibly due to the penetration enhancing effect of ethanol. The skin permeation of indomethacin was substantially influenced by the gel pH, exhibiting a maximum at pH 4.

• Neonatal Medicine
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• v.18 no.2
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• pp.228-233
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• 2011

Purpose: The aim of our study was to compare the efficacy and safety of ibuprofen and indomethacin in the prophylaxis of patent ductus arteriosus (PDA) in preterm infants and to determine whether ibuprofen could be an alternative agent in prophylactic use. Methods: A retrospective study including 37 preterm infants <1,500 g of birth weight, <34 weeks of gestation, whom were administrated indomethacin (n=17; January 2009-December 2009) or ibuprofen (n=20; January 2010-February 2011) within 24 hr after birth was conducted. The rate of ductal closure, need for surgical ligation, clinical outcomes such as necrotizing enterocolitis, intraventricular hemorrhage, bronchopulmonary dysplasia, retinopathy of prematurity (ROP) and death rate were compared. Results: There were no statistically significant differences between the two groups in mean gestational age, mean birth weight, Apgar score, sex, type of delivery, maternal dexamethasone treatment, frequency and duration of ventilator and surfactant treatment. The closure of PDA on day 7 of life was in 19 of 20 infants of the ibuprofen group and 13 of 17 infants of the indomethacin group (P=0.159). Between the two groups, there were no significant differences with respect to clinical outcomes. Conclusion: Ibuprofen has similar effects to indomethacin in the rate of PDA closure. Our study demonstrates that prophylactic ibuprofen is relatively effective without significant differences with respect to clinical outcomes compared with indomethacin. Therefore, ibuprofen may be used as an alternative agent in the prophylaxis of PDA in preterm infants.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.1
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• pp.75-82
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• 1999

It has been reported that activation of sphingomyelin pathway and nonsteroidal anti-inflammatory drugs (NSAIDS) inhibit the promotion of colon carcinoma. Ceramide, a metabolite of sphingomyelin, and indomethacin were shown to induce apoptosis in colon carcinoma cells. However, the mechanisms of ceramide- and indomethacin-induced apoptosis in the colon carcinoma cells are not clearly elucidated. Recent studys showed that indomethacin-induced apoptosis in colon cancer cells through the cyclooxygenase-independent pathways, and that may be mediated by generation of ceramide. In this study, we compared effects of ceramide and indomethacin on important modulators of apoptotic processes in HT29 cells, a human colon cancer cell line. Ceramide and indomethacin induced apoptosis dose- and time- dependently. Ceramide and indomethacin increased stress-activated protein kinase (SAPK) activity, and decreased mitogen-activated protein kinase (MAPK) activity. The expression of Bak was increased by the treatment of ceramide and indomethacin. The expression of other Bcl-2 related proteins (Mcl-1, $Bcl-X_L,$ Bax) which were known to be expressed in colon epithelial cells was not changed during the ceramide- and indomethacin-induced apoptosis. Our results suggest that ceramide and indomethacin share common mechanisms for induction of apoptosis in HT29 cells.