• The Korean Journal of Physiology and Pharmacology
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• 제16권6호
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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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• 제18권3호
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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.

• 약학회지
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• 제43권2호
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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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• 제12권3호
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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.

• 약학회지
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• 제33권3호
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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.

• 대한치과교정학회지
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• 제26권2호
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• pp.163-174
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• 1996

본 실험은 서로 다른 기전으로 골흡수를 억제한다고 추정되는 약제인 bisphosphonate와 indomethacin을 백서에 투여한 후 교정력을 이용한 치아이동시 약제가 골개조에 미치는 영향을 밝히고자 시행되었다. 동일한 조건에서 사육된 체중 260-300g의 웅성백서(Sprague-Dawley계)를 대조군, bisphosphonate 투여군 및 indomethacin 투여군으로 분류하고 각 군은 다시 장치를 장착한 실험측과 장치를 장착하지 않은 대조측으로 분류하였다. Bisphosphonate(6.3mg/kg,$2.52x10^{-2}mol/L$)와 indomethacin(9mg/kg, $2.52x10^{-2}mol/L$)은 교정장치 장착 6시간 전, 1시간 전 및 24시간 후에 복강내 주사하였으며, 교정력이 가해진 시점으로부터 72시간이 경과한 후 파골세포수를 측정하고 조직학적인 성상을 관찰하였다. 또한 혈액을 채취한 후 혈청 acid phosphatase 및 lactate dehydrogenase 양을 측정하여 다음과 같은 성적을 얻었다. 실험측의 파골세포수는 장치장착 1시간 전에 투여한 bisphosphonate군과 indomethacin군에서 가장 적게 나타났으며, 다른 시간의 약물 투여군은 대조군과 차이가 없었다. 대조측의 파골세포수는 실험측보다 현저히 적게 나타났으며, 대조군 및 약물투여군간에 차이가 없었다. 대조군과 6시간 전 및 24시간 후에 투여한 indomethacin군은 심한 골흡수 양상을 보인 반면, 1시간전 indomethacin군 및 모든 bisphosphonate군에서는 골흡수의 정도가 적었다. 파골세포의 주름변연과 투명대는 대조군 및 indomethacin군에서 가장 뚜렷하게 나타났으며, bisphosphonate 투여군에서는 일부 파골세포들이 무딘 세포돌기만을 내거나 골표면에 부착하지 않고 있는 경우가 많았다. Bisphosphonate와 indomethacin 투여군 모두에서 acid phosphatase 및 lactate dehydrogenase 값이 대조군보다 낮았으며, acid phosphatase 값은 bisphosphonate군이 indomethacin군보다 낮았으나 lactate dehydrogenase 값은 차이가 없었다. 이상의 결과로 bisphosphonate는 파골세포의 수 및 대사활동을 감소시키며 indomethacin은 파골세포의 수를 감소시킴을 알 수 있었다. 또한 두 약물을 비교하면 bisphosphonate는 indomethacin에 비해 골흡수 억제효과가 더 크며 투여시간에 따른 제약도 더 적은 것으로 사료된다.

• Journal of Microbiology and Biotechnology
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• 제14권5호
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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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• 제25권2호
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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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• 제18권2호
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• pp.228-233
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• 2011

목적: Indomethacin은 미숙아 동맥관 개존증의 예방적 용법 및 치료적 용법에 사용되어 왔다. 하지만 최근에는 indomethacin의 국내 보급이 중단됨에 ibuprofen이 사용되고 있다. Ibuprofen은 동맥관 폐쇄에 indomethacin만큼 효과적이며 부작용은 적은 것으로 알려져 있다. 그러나 ibuprofen의 예방적 용법에 관한 연구는 많지 않다. 본 연구에서는 미숙아에서 동맥관 개존증의 예방적 치료에 대한 ibuprofen의 효과와 안정성을 indomethacin과 비교하여 분석하고자 하였다. 방법: 2009년 1월부터 2009년 12월, 그리고 2010년 1월부터 2011년 2월까지 두 기간동안 3개의 참여 대학병원 신생아 중환자실에 입원한 34주 미만, 1,500 g 미만의 신생아 중에서 생후 24시간 이내에 indomethacin이나 ibuprofen이 예방적 목적으로 투여된 환자를 대상으로 하여 의무기록을 후향적으로 검토하였다. 두 군간의 동맥관 폐쇄에 대한 효과와 주산기 합병증의 발생 정도를 조사하였다. 결과: 두 군간에 환아의 성별, 재태 연령, 출생체중, 분만 방법, 1분 및 5분 Apgar 점수, 산모의 steroid 사용 여부, 폐 표면활성제 사용 여부 및 인공호흡기 사용여부 및 사용기간에 있어 유의한 차이는 없었다. 생후 7일에 시행한 심초음파 검사에서 indomethacin군은 17명 중 13명, ibuprofen군은 20명 중 19명이 동맥관의 폐쇄를 보였다. 총 입원 기간 외에 주산기 합병증의 빈도는 두 군간의 유의한 차이가 없었다. 결론: Ibuprofen의 예방적 사용은 동맥관 폐쇄에 효과적이며 주산기 합병증 측면에서 유의한 부정적인 차이가 없었다. 따라서 indomethacin을 대체하여 ibuprofen의 사용을 고려해 볼 수 있겠다.

• The Korean Journal of Physiology and Pharmacology
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• 제3권1호
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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.