BACKGROUND Post-endoscopic retrograde cholangiopancreatography pancreatitis(PEP)is a prevalent and potentially serious complication in patients undergoing endoscopic retrograde cholangiopancreatography.AIM To comprehe...BACKGROUND Post-endoscopic retrograde cholangiopancreatography pancreatitis(PEP)is a prevalent and potentially serious complication in patients undergoing endoscopic retrograde cholangiopancreatography.AIM To comprehensively assess the efficacy of indomethacin therapy in reducing PEP risk.METHODS We searched PubMed,EMBASE,Scopus,and Cochrane Library databases to identify randomized controlled trials(RCTs)that compared rectal indomethacin with a control group to prevent PEP.Duplicates were removed,and studies were included based on the established inclusion criteria.We used the Cochrane Collaboration’s tool to assess the risk of bias in the RCTs.A random-effects model was applied to produce pooled risk ratios(RRs)with 95%confidence intervals(CIs).RESULTS We included a total of 30 RCTs involving 16977 patients.Compared to the control group,rectal indomethacin showed comparable rates of overall PEP(PEP;RR=0.85,95%CI:0.69-1.04,I2=79%)with no statistically significant difference of RR in mild(RR=0.92,95%CI:0.74-1.14),moderate(RR=0.78,95%CI:0.59-1.02),or severe PEP(RR=1.12,95%CI:0.75-1.67).There was also no difference in cases of adverse events(RR=0.97,95%CI:0.69-1.35),abdominal pain(RR=1.14,95%CI:0.80-1.62),bleeding(RR=1.07,95%CI:0.70-1.63),or mortality(RR=0.86,95%CI:0.56-1.33)between the two groups.Subgroup analyses were also performed.CONCLUSION Rectal indomethacin appears to be safe and may offer benefit in selected high-risk patients,though findings should be interpreted with caution due to high heterogeneity.展开更多
The ongoing development of small molecule drugs underscores the urgent need for novel excipients to formulate poorly soluble drug candidates.Cucurbit[7]uril(CB[7])possesses high binding affinities for a variety of mol...The ongoing development of small molecule drugs underscores the urgent need for novel excipients to formulate poorly soluble drug candidates.Cucurbit[7]uril(CB[7])possesses high binding affinities for a variety of molecular vips.However,its moderate water solubility limits broader application.Here we report the synthesis of three CB[7]derivatives M1-M3 by modifying an average of 4.2,5.5,and 5.9 sulfonatopropoxy groups onto their"equator"carbons.Compared to CB[7],their water-solubility increased by at least 26.6-,23.6-,and 19.2-fold,respectively,while the maximum tolerated doses(MTD)of M1 and M2 improved by 2.5-and 2.3-fold.Phase solubility diagram studies demonstrate that M1 and M2 significantly enhance the water-solubility of eighteen poorly soluble drugs.In vivo experiments in rat complete Freund's arthritis reveal that M1 not only improves the anti-inflammatory efficacy of indomethacin by up to 52%,but also substantially reduces its side effect of gastric ulcer.展开更多
We studied the effect of two independent variables, the pectin/calcium chloride weight ratio and the overall matrix weight in HPMC/pectin/calcium matrix tablet, on the release of indomethacin. A two-factor 5-level cen...We studied the effect of two independent variables, the pectin/calcium chloride weight ratio and the overall matrix weight in HPMC/pectin/calcium matrix tablet, on the release of indomethacin. A two-factor 5-level central composite experimental design was employed. Responses of the Peppas correlation parameters n and K and the 10% release time （T0.1） were optimized by response surface methodology. Significant effect of the independent variables on the biphasic release parameters, n and K, was observed. N, K and T0.1 were well fitted with the second-order quadratic equations rather than linear equations. Moreover, the mathematic fitting and the response surfaces showed significant cross-interaction between the pectin/calcium chloride ratio and the overall matrix weight. The optimal formulation with larger n, longer T0.1 and smaller K consisted of medium pectin/calcium chloride ratio around 1.0 and medium matrix weight around 200 mg. Validation studies on the optimal formulations showed good predictability of the n, K and T0.1 values with biases within the range of-7.33% and 6.26%. Our results support that central composite design can be used to optimize drug release from HPMC/pectin/calcium matrix tablet with high predictability.展开更多
AIM: Mechanisms underlying the chemopreventive effects of cyclooxygenase (COX) inhibitors remain elusive. We have previously shown that celecoxib but not indomethacin could prevent carcinogen-induced gastric cancer de...AIM: Mechanisms underlying the chemopreventive effects of cyclooxygenase (COX) inhibitors remain elusive. We have previously shown that celecoxib but not indomethacin could prevent carcinogen-induced gastric cancer development in Wistar rats. This chemopreventive effect appeared to be independent of COX-2 and prostaglandin (PG) E2 suppression since the lowest PGE2 was obtained in indomethacin group.This study compared the cell kinetic changes in stomachs of rats after treatment with celecoxib (5, 10, 20 mg/(kg·d)) or indomethacin (3 mg/(kg·d)) to gain more insights into the chemopreventive mechanism.METHODS: The apoptosis and proliferation indexes in gastric tumor, adjacent non-cancer tissues and normal gastric tissues were determined. Apoptosis was quantified by apoptotic nuclei counting and TUNEL, whereas proliferation was determined by Ki67 immunostaining.RESULTS: Treatment with either celecoxib or indomethacin inhibited gastric tumor proliferation by more than 65% (P＜0.02). However, celecoxib caused a dose-dependent increase in apoptosis (P＜0.05) which was not seen in indomethacin-treated tumors (P = 0.54). The highest apoptosis to proliferation ratio was seen in tumors treated with celecoxib at 10 mg/(kg·d). Treatment with this dose of celecoxib was associated with the lowest incidence of gastric cancer development.CONCLUSION: Our findings suggest that the difference in chemopreventive effects of indomethacin and celecoxib in this animal model of gastric carcinogenesis is largely due to the differential cell kinetic changes, which does not correlate with the degree of COX-2 and PG suppression.展开更多
AIM: To investigate the effectiveness of rectally administered indomethacin in the prophylaxis of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis and hyperamylasaemia in a multicentre study.
AIM: It has been reported that regular consumption of nonsteroidal anti-inflammatory drugs like indomethacin decreases the incidence and mortality rate of a number of gastrointestinal cancers. We aimed to explore the ...AIM: It has been reported that regular consumption of nonsteroidal anti-inflammatory drugs like indomethacin decreases the incidence and mortality rate of a number of gastrointestinal cancers. We aimed to explore the efficacy and possible mechanisms of indomethacin on tumor growth and tumor angiogenesis of human colon cancer xenografts in nude mice. METHODS: MTT (thiazolyl blue) assay was used to assess the effect of indomethacin on cultured human colorectal cancer cell line HCT116. HCT116 cells were inoculated subcutaneously into BALB/c-nu/nu mice. After oral administration of indomethacin, 3 mg/kg·d for 4 wk, animals were sacrificed by cervical dislocation. Immunohistochemical staining was employed to determine the microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression in tumor tissues. RESULTS: Indomethacin, a non-selective COX inhibitor, significantly decreased the viability of HCT116 cells in a dose-dependent manner (P<0.05) with 50% inhibition at approximately 318.2±12.7 μmol/L Growth of HCT116 cell tumor was significantly suppressed by indomethacin. The tumor volume was significantly decreased in the treated group (458.89±32.07 mm3) compared to the control group (828.21±31.59 mm3) (P<0.05). The MVD of the treated group (19.50±5.32) was markedly decreased compared to the control group (37.40±4.93) (P<0.001). The VEGF expression of the treated group (1.19±0.17) was obviously reduced as compared to the control group (1.90±0.48) (P<0.01). The decrease in MVD was positively correlated with the decrease of VEGF expression (rs = 0.714, P<0.05). We did not see gastrointestinal complications in the treated group and no differences were noted in the body weight of the mice between the two groups throughout the study CONCLUSION: Indomethacin can significantly decrease the viability of cultured HCT116 cells and retard human colorectal HCT116 cell tumor growth via inhibiting tumor angiogenesis, which might be through reduction of VEGF expression.展开更多
OBJECTIVE： Carica papaya is an important fruit with its seeds used in the treatment of ulcer in Nigeria This study investigated the anti-ulcerogenic and antioxidant activities of aqueous extract of Carica papaya seed...OBJECTIVE： Carica papaya is an important fruit with its seeds used in the treatment of ulcer in Nigeria This study investigated the anti-ulcerogenic and antioxidant activities of aqueous extract of Carica papaya seed against indomethacin-induced peptic ulcer in male rats. METHODS： Thirty male rats were separated into 6 groups （A-F） of five rats each. For 14 d before ulcer induction with indomethacin, groups received once daily oral doses of vehicle （distilled water）, cimetidine 200 mg/kg body weight （BW）, or aqueous extract of C. papaya seed at doses of 100, 150 or 200 mg/kg BW （groups A, B, C, D, E and F, respectively）. Twenty-four hours after the last treatment, groups B, C, D, E and F were treated with 100 mg/kg BW of indomethacin to induce ulcer formation. RESULTS： Carica papaya seed extract significantly （P〈0.05） increased gastric pH and percentage of ulcer inhibition relative to indomethacin-induced ulcer rats. The extract significantly （P〈0.05） decreased gastric acidity, gastric acid output, gastric pepsin secretion, ulcer index and gastric secretion volume relative to group B. These results were similar to that achieved by pretreatment with cimetidine. Specific activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase in the extract-treated groups （D, E and F） were increased significantly over the group B （P〈0.05）. Pretreatment with the seed extract protected rats from the indomethacin-mediated decrease in enzyme function experienced by the group B. Similarly, indomethacin-mediated decrease in reduced glutathione level and indomethacin-mediated increase in malondialdehyde were reversed by Carica papaya extract. CONCLUSION： In this study, pretreatment with aqueous extract of Carica papaya seed exhibited anti- ulcerogenic and antioxidant effects, which may be due to the enhanced antioxidant enzymes.展开更多
Our study aimed to investigate the protective effects of Holothurian intestines(HI) on NSAIDs-induced gastric mucosal damage and the possible mechanism. At first, 60 male Wistar rats were induced of gastric lesions wi...Our study aimed to investigate the protective effects of Holothurian intestines(HI) on NSAIDs-induced gastric mucosal damage and the possible mechanism. At first, 60 male Wistar rats were induced of gastric lesions with indomethacin(IDM, 30 mg kg^(-1)). The rats were pretreated for 15 consecutive days with saline, sucralfate, or HI(0.4g kg^(-1) d-1, 0.8 g kg^(-1) d^(-1) and 1.6 g kg^(-1) d^(-1)) prior to IDM treatment, followed by evaluations of macroscopic damage and microscopic features; and investigation of the levels of inflammatory cytokines, oxidative stress parameters, gastric mucosal prostaglandin E2(PGE2) and total hexosamine in tissues. The expression of COX-1 and COX-2 m RNA in the gastric tissue were determined by quantitative polymerase chain reaction(q PCR). Pathological gastric ulcer indexes, levels of pro-inflammatory cytokines(IL-1β, IL-17, TNF-α) and lipid peroxidation were significantly decreased in HI-treated groups, whereas the levels of protective factors(TGF-β, GSH, SOD activity and PGE2) were significantly elevated especially in the group with HI 1.61 g kg^(-1) d^(-1)(P < 0.05). Furthermore, the expression of COX-2 mRNA decreased significantly in HI groups(P < 0.05). The study investigates that holothurian intestines may act as a kind of marine medicine which have protective effect on IDM-induced gastric ulcer, which could be a dietary preventive agent for the prevention of gastric damage.展开更多
AIM： To investigate the mucosal protective effect and the mechanisms of action of the anti-ulcer drug irsogladine maleate in gastric injury induced by indomethacin in rats. METHODS： Gastric mucosal injury was induce...AIM： To investigate the mucosal protective effect and the mechanisms of action of the anti-ulcer drug irsogladine maleate in gastric injury induced by indomethacin in rats. METHODS： Gastric mucosal injury was induced in male Hos：Donryu rats by oral administration of indomethacin at a dose of 48 mg/kg. One hour before indomethacin treatment, animals were orally pretreated with irsogladine maleate at doses of 1 mg/kg, 3 mg/kg or 10 mg/kg. Four hours after indomethacin administration, the animals were sacrificed and their stomachs were rapidly removed and processed for the evaluation of gastric mucosal damage and the determination of the concentrations of tumor necrosis factor-α （TNF-α）, interleukin-1β （IL-1β）, IL-8 and myeloperoxidase （MPO） in mucosal tissues. RESULTS： Linear hemorrhagic mucosal lesions were observed primarily in the glandular stomach 4 h alter oral administration of indomethacin. Pretreatment with irsogladine maleate markedly reduced the number and severity of these lesions in a dose-dependent manner. The mucosal concentrations of proinflammatory cytokines （TNF-α, IL-1β, and IL-8） and MPO, which indicates the degree of mucosal infiltration by neutrophils, increased concomitantly with the occurrence of gastric injury in the indomethacintreated rats. Pretreatment with irsogladine maleate significantly decreased the levels of these inflammatory factors in gastric tissue elicited by indomethacin.CONCLUSION： The mucosal protective effects afforded by irsogladine maleate on gastric injury induced by indomethacin are mediated by inhibition of mucosal proinflammatory cytokine production and neutrophil infiltration, leading to suppression of mucosal inflammation and subsequent tissue destruction.展开更多
Objective:To investigate the restorative effect of Pterocarpus erinaceus(P.erinaceus) and homopterocarpin.an isoflavonoid isolated from it.on indomethacin-indueed disruption in gastric homeostasis in rats.Methods:Adul...Objective:To investigate the restorative effect of Pterocarpus erinaceus(P.erinaceus) and homopterocarpin.an isoflavonoid isolated from it.on indomethacin-indueed disruption in gastric homeostasis in rats.Methods:Adult rats were dn ided into five groups and lasted for 48 h before treatment.Group I received olive oil(vehicle),group 2 received 25 ing/kg indomethaein while groups 3-5 received cimetidine(100 mg/kg).lioniopterocarpin(25 mg/kg) and P.erinaceus ethanolie stem hark extract(100 mg/kg) respectively.After 1 h.all the groups except group 2 were administered 25 mg/kg of indomethacin.One hour later,the rats were sacrificed and the ulcer index and other gaslroprotective indices were evaluated.Results:Indomethacin caused significant injury to the stomach of the rats as reflected in the ulcer indices(9.0±1.4) as compared with that of control(2.0±0.0).Equally,there were significant increases in gastric acid concentration and malondialdehvde level in the stomachs of the ulcerated animals compared with the control.However mucus content,reduced gluthatione level and gastric pH were significantly reduced in the ulcerated animals compared with the control.Pretreatment with either Pterocarpus bark extract or homopterocarpin reversed the effects of indomethaein on the evaluated parameters.Conclusions:These results indicate that both homopterocarpin and Plerocarpus extract offered gastroprotection against indomethacin-induced ulcer by antioxidative mechanism and the modulation of gastric homeostasis.The results also suggest that homopterocarpin might he responsible for.or contribute to the antiulcerogenic property of P.erinaceus.展开更多
OBJECTIVE： To determine the role of a pharmacokinetic interaction in the protective effect of curcumin against the gastric damage induced by indomethacin administration as such or as its prodrug acemetacin. METHODS：...OBJECTIVE： To determine the role of a pharmacokinetic interaction in the protective effect of curcumin against the gastric damage induced by indomethacin administration as such or as its prodrug acemetacin. METHODS： Wistar rats orally received single dose of indomethacin （30 mg/kg） with and without curcumin （30 mg/kg）; gastric injury was evaluated by determining the total damaged area. Additional groups of rats received an oral single dose of indomethacin （30 mg/kg） or its prodrug acemetacin （34.86 mg/kg） in the presence or absence of curcumin （30 mg/kg）. Indomethacin and acemetacin concentrations in plasma from blood draws were determined by high-performance liquid chromatography Plasma concentration-against-time curves were constructed, and bioavailability parameters, maximal concentration （Cmax） and area under the curve to the last sampling time （AUC0_t） were estimated. RESULTS： Concomitant administration of indomethacin and curcumin resulted in a significantly reduced gastric damage compared to indomethacin alone. However, co-administration of curcumin did not produce any significant alteration in the bioavailability parameters of indomethacin and acemetacin after administration of either the active compound or the prodrug. CONCLUSION： Curcumin exhibits a protective effect against indomethacin-induced gastric damage, but does not produce a reduction of the bioavailability of this nonsteroidal anti-inflammatory drug, indomethacin. Data thus suggest that a pharmacokinetic mechanism of action is not involved in curcumin gastroprotection.展开更多
KangFuXinYe(KFX),the ethanol extract of the dried whole body of Periplaneta americana,is a well-known important Chinese medicine preparation that has been used to treat digestive diseases such as gastric ulcers for ma...KangFuXinYe(KFX),the ethanol extract of the dried whole body of Periplaneta americana,is a well-known important Chinese medicine preparation that has been used to treat digestive diseases such as gastric ulcers for many years in China.However,its therapeutic effect and mechanism are not yet well understood.Thus,the aim of this study was to investigate the gastroprotective effects of KangFuXinYe(KFX)in indomethacin-induced gastric damage.Rats were randomly divided into six groups as follows:control,treated with indomethacin(35 mg·kg^-1),different dosages of KFX(2.57,5.14 and 10.28 mL·kg^-1,respectively)plus indomethacin,and sucralfate(1.71 mL·kg^-1)plus indomethacin.After treatment,rat serum,stomach and gastric homogenates were collected for biochemical tests and examination of histopathology firstly.Rat serum was further used for metabolomics analysis to research possible mechanisms.Our results showed that KFX treatment alleviated indomethacin-induced histopathologic damage in rat gastric mucosa.Meanwhile,its treatment significantly increased cyclooxygenase-1(COX-1),prostaglandin E2(PGE2)and epidermal growth factor(EGF)levels in rat serum and gastric mucosa.Moreover,KFX decreased cyclooxygenase-2(COX-2)and interleukin-6(IL-6)levels.Nine metabolites were identified which intensities significantly changed in gastric damage rats,including 5-hydroxyindoleacetic acid,indoxylsulfuric acid,indolelactic acid,4-hydroxyindole,pantothenic acid,isobutyryl carnitine,3-methyl-2-oxovaleric acid,sphingosine 1-phosphate,and indometacin.These metabolic deviations came to closer to normal levels after KFX intervention.The results indicate that KFX(10.28 mL·kg^-1)exerts protective effects on indomethacin-induced gastric damage by possible mechanisms of action(regulating tryptophan metabolism,protecting the mitochondria,and adjusting lipid metabolism,and reducing excessive indomethacin).展开更多
AIM: To study the effects of indomethacin on the isolated transverse and longitudinal rat gastric fundus strips.METHODS: The strips were suspended in an organ bath containing oxygenated Krebs solution, and contractile...AIM: To study the effects of indomethacin on the isolated transverse and longitudinal rat gastric fundus strips.METHODS: The strips were suspended in an organ bath containing oxygenated Krebs solution, and contractile responses to electrical field stimulation were recorded on a physiograph in an isotonic manner after administration of cumulative concentrations of indomethacin. The effects of indomethacin on the strips pretreated with KATP channel modulators, diazoxide and glybenclamide were studied.RESULTS: Treatment of the transverse strips with indomethacin resulted in a concentration-dependent inhibitory response. In longitudinal strips, biphasic responses were seen, which included a stimulatory response at low concentrations of indomethacin, followed by an inhibitory response at higher concentrations.Diazoxide pre-treatment inhibited the stimulatory response of longitudinal strips. Glybenclamide pre-treatment not only blocked inhibitory effect of the low concentrations of indomethacin on transverse strips, but also increased the amplitude of contractions. Moreover, the drug decreased the amplitude of contractions in longitudinal strips.CONCLUSION: Responses of the isolated longitudinal and transverse rat gastric fundus strips to indomethacin are not similar, and are influenced by KATP channel modulators.展开更多
AIM: Vasodilatation and increased capillary permeability have been proposed to be involved in the pathogenesis of acute and chronic form of hepatic encephalopathy. Prostacyclin (PGI2) and nitric oxide (NO) are importa...AIM: Vasodilatation and increased capillary permeability have been proposed to be involved in the pathogenesis of acute and chronic form of hepatic encephalopathy. Prostacyclin (PGI2) and nitric oxide (NO) are important contributors to hyperdynamic circulation in portal hypertensive states. Our previous study showed that chronic inhibition of NO had detrimental effects on the severity of encephalopathy in thioacetamide (TAA)-treated rats due to aggravation of liver damage. To date, there are no detailed data concerning the effects of PGI2 inhibition on the severity of hepatic encephalopathy during fulminant hepatic failure. METHODS: Male Sprague-Dawley rats weighing 300-350 g were used. Fulminant hepatic failure was induced by intraperitoneal injection of TAA (350 mg/(kg·d) for 3 d. Rats were divided into two groups to receive intraperitoneal injection of indomethacin (5 mg/(kg·d), n = 20) or normal saline (N/S, n = 20) for 5 d, starting 2 d before TAA administration. Severity of encephalopathy was assessed by the counts of motor activity measured with Opto-Varimex animal activity meter. Plasma tumor necrosis factor-α (TNF-α, an index of liver injury) and 6-keto-PGF1α (a metabolite of PGI2) levels were measured by enzyme-linked immunosorbent assay. RESULTS: As compared with N/S-treated rats, the mortality rate was significantly higher in rats receiving indomethacin (20% vs5%, P<0.01). Inhibition of PGI2 created detrimental effects on total movement counts (indomethacin vs N/S: 438±102 vs 841±145 counts/30 min, P<0.05). Rats treated with indomethacin had significant higher plasma levels of TNPa (indomethacin vs N/S: 22±5 vs 10±1 pg/mL, P<0.05) and lower plasma levels of 6-keto-PGF1α (P<0.001), but not total bilirubin or creatinine (P>0.05), as compared with rats treated with N/S. CONCLUSION: Chronic indomethacin administration has detrimental effects on the severity of encephalopathy in TAA-treated rats and this phenomenon may be attributed to the aggravation of liver injury. This study suggests that PGI2 may provide a protective role in the development of fulminant hepatic failure.展开更多
We applied a combination of inorganic mesoporous silica material,frequently used as drug carriers,and a natural organic polymer alginate(ALG),to establish a sustained drug delivery system for the poorly water-soluble ...We applied a combination of inorganic mesoporous silica material,frequently used as drug carriers,and a natural organic polymer alginate(ALG),to establish a sustained drug delivery system for the poorly water-soluble drug Indomethacin(IND).Mesoporous silica nanospheres(MSNs)were synthesized using an organic template method and then functionalized with aminopropyl groups through postsynthesis.After drug loading into the pores of aninopropyl functionalized MSNs(AP-MSNs),IND loaded AP-MSNs(IND-AP-MSNs)were encapsulated by ALG through the ionic interaction.The effects of surface chemical groups and ALG layer on IND release were systematically studied using scanning electron microscopy(SEM),transmission electron microscopy(TEM),nitrogen adsorption,zetapotential analysis and TGA analysis.The surface structure and surface charge changes of the ALG encapsulated AP-MSNs(ALG-AP-MSNs)were also investigated.The results showed that sustained release of IND from the designed drug delivery system was mainly due to the blockage effect from the coated ALG.We believe that this combination will help designing oral sustained drug delivery systems for poorly water-soluble drugs.展开更多
Effects of two types of intrauterine device (IUD) on the prostaglandins and endothelin (ET) in uterus and on the endometrial morphology in rats and rabbits, and Cu 2+ releasing amounts of both IUDs in vitro w...Effects of two types of intrauterine device (IUD) on the prostaglandins and endothelin (ET) in uterus and on the endometrial morphology in rats and rabbits, and Cu 2+ releasing amounts of both IUDs in vitro were observed. The results showed that the inhibiting action of the indomethacin releasing copper IUD (FICu IUD) on the PGI 2 was stronger than that on the TXA 2, the ratio of 6 keto PGF 1α /TXB 2 was reduced with the increase of the doses. There were significant differences between the groups. The FICu IUD could inhibit the rising of the ET level and lighten the endometrial impairment caused by the FCu IUD, and promote copper ion release. It was suggested that indomethacin released by FICu IUD could effectively reduce abnormal uterine bleeding.展开更多
Topical administration is the most common and acceptable use for the treatment of ocular disease.However,the major problem of ocular drug delivery is the rapid drug elimination from the pre-ocular area leading to poor...Topical administration is the most common and acceptable use for the treatment of ocular disease.However,the major problem of ocular drug delivery is the rapid drug elimination from the pre-ocular area leading to poor ocular bioavailability[1].Nanostructure lipid carriers(NLC)possess a significant enhancement in ocular bioavailability by increasing the permeability and mucoadhesive property[2].In this study,indomethacin(IND),non-steroidal anti-inflammatory,was used as a model drug[3].展开更多
AIM: To establish the two-dimensional gel electrophoresis (2-DE) profiles of indomethacin (IN)-treated human colon cancer cell line HCT116, and to provide a new way to study its anti-tumor molecular mechanism through ...AIM: To establish the two-dimensional gel electrophoresis (2-DE) profiles of indomethacin (IN)-treated human colon cancer cell line HCT116, and to provide a new way to study its anti-tumor molecular mechanism through analyzing a variety of protein maps.METHODS: Two-DE profiles of HCT116 were established in IN-treated and untreated groups. Total proteins were separated by immobilized pH gradient-based 2-DE. The gels were stained by silver, scanned by ImageScanner,and analyzed with Image Master software.RESULTS: Clear background, well-resolved and reproducible 2-DE patterns of HCT116 cells were acquired in IN-treated and untreated group. The average deviation of spot position was 0.896±0.177 mm in IEF direction and 1.106±0.289 mm in SDS-PAGE direction respectively. In IN-treated group,1 169±36 spots were detected and 1 061±32 spots were matched, the average matching rate was 90.6% in three gels. In untreated group, 1 256±50 spots were detected and 1 168±46 spots were matched, the average matching rate was 93.0% in three gels. Forty-five differential protein spots were displayed between IN-treated and untreated groups. Of which, 34 protein spots decreased and 9showed higher expression in IN-treated group, and only two protein spots showed an expression in untreated cells.CONCLUSION: Two-DE profiles of IN-treated and untreated HCT116 cells were established. Apparent 45 different protein spots were detected in IN-treated and untreated HCT116 cells. The analysis on differential protein spots may serve as a new way to study the molecule mechanism of IN-treated colon cancer.展开更多
Objective： To evaluate the renoprotection effects of non-steroidal anti-inflammatory drugs （NSAIDs） in renal ischemia-reperfusion injury （IRI） and the cyclooxygenase （COX）-1/2 blockade association by indomethac...Objective： To evaluate the renoprotection effects of non-steroidal anti-inflammatory drugs （NSAIDs） in renal ischemia-reperfusion injury （IRI） and the cyclooxygenase （COX）-1/2 blockade association by indomethacin （IMT） in the mice model. Methods： After the left renal pedicle of mice was clamped, IMT was administrated by intraperitoneal injection with four doses： 1, 3, 5, and 7 mg/kg. Blood and kidney samples were collected 24 h after IRI. The renal functions were assayed by the cytokines and serum creatinine （SCr） using enzyme-linked immunosorbent assay （ELISA） kits. Kidney samples were analyzed by hematoxylin and eosin （H＆E） and immunohistochemistry stainings. Results： The mice administered with 5 mg/kg IMT had a marked reduction in SCr and significantly less tubular damage The tumor necrosis factor a （TNF-α） activity in renal homogenates and interleukin 6 （IL-6） activity in serum had a marked reduction at doses of 5 and 7 mg/kg IMT. The administration of 3 and 5 mg/kg IMT had a marked reduction in the ratio of thromboxane B2 to 6-keto-prostaglandin F1α. COX-1 and COX-2 stainings were weaker in 5 mg/kg IMT groups than that in the other groups. Conclusions： There was a dose response in the IMT function of renal IRI in mice, and IMT had a protective effect in a certain dose range. The effect of IMT on mice IRI was related to COX-1/2 blockades.展开更多
文摘BACKGROUND Post-endoscopic retrograde cholangiopancreatography pancreatitis(PEP)is a prevalent and potentially serious complication in patients undergoing endoscopic retrograde cholangiopancreatography.AIM To comprehensively assess the efficacy of indomethacin therapy in reducing PEP risk.METHODS We searched PubMed,EMBASE,Scopus,and Cochrane Library databases to identify randomized controlled trials(RCTs)that compared rectal indomethacin with a control group to prevent PEP.Duplicates were removed,and studies were included based on the established inclusion criteria.We used the Cochrane Collaboration’s tool to assess the risk of bias in the RCTs.A random-effects model was applied to produce pooled risk ratios(RRs)with 95%confidence intervals(CIs).RESULTS We included a total of 30 RCTs involving 16977 patients.Compared to the control group,rectal indomethacin showed comparable rates of overall PEP(PEP;RR=0.85,95%CI:0.69-1.04,I2=79%)with no statistically significant difference of RR in mild(RR=0.92,95%CI:0.74-1.14),moderate(RR=0.78,95%CI:0.59-1.02),or severe PEP(RR=1.12,95%CI:0.75-1.67).There was also no difference in cases of adverse events(RR=0.97,95%CI:0.69-1.35),abdominal pain(RR=1.14,95%CI:0.80-1.62),bleeding(RR=1.07,95%CI:0.70-1.63),or mortality(RR=0.86,95%CI:0.56-1.33)between the two groups.Subgroup analyses were also performed.CONCLUSION Rectal indomethacin appears to be safe and may offer benefit in selected high-risk patients,though findings should be interpreted with caution due to high heterogeneity.
基金National Natural Science Foundation of China(Nos.21921003 and 22201293)the National Key R&D Program of China(No.2023YFC3503400)for financial support。
文摘The ongoing development of small molecule drugs underscores the urgent need for novel excipients to formulate poorly soluble drug candidates.Cucurbit[7]uril(CB[7])possesses high binding affinities for a variety of molecular vips.However,its moderate water solubility limits broader application.Here we report the synthesis of three CB[7]derivatives M1-M3 by modifying an average of 4.2,5.5,and 5.9 sulfonatopropoxy groups onto their"equator"carbons.Compared to CB[7],their water-solubility increased by at least 26.6-,23.6-,and 19.2-fold,respectively,while the maximum tolerated doses(MTD)of M1 and M2 improved by 2.5-and 2.3-fold.Phase solubility diagram studies demonstrate that M1 and M2 significantly enhance the water-solubility of eighteen poorly soluble drugs.In vivo experiments in rat complete Freund's arthritis reveal that M1 not only improves the anti-inflammatory efficacy of indomethacin by up to 52%,but also substantially reduces its side effect of gastric ulcer.
基金Shanghai Municipal Committee of Sciencc and Tcchnology (Grant No.024319114).
文摘We studied the effect of two independent variables, the pectin/calcium chloride weight ratio and the overall matrix weight in HPMC/pectin/calcium matrix tablet, on the release of indomethacin. A two-factor 5-level central composite experimental design was employed. Responses of the Peppas correlation parameters n and K and the 10% release time （T0.1） were optimized by response surface methodology. Significant effect of the independent variables on the biphasic release parameters, n and K, was observed. N, K and T0.1 were well fitted with the second-order quadratic equations rather than linear equations. Moreover, the mathematic fitting and the response surfaces showed significant cross-interaction between the pectin/calcium chloride ratio and the overall matrix weight. The optimal formulation with larger n, longer T0.1 and smaller K consisted of medium pectin/calcium chloride ratio around 1.0 and medium matrix weight around 200 mg. Validation studies on the optimal formulations showed good predictability of the n, K and T0.1 values with biases within the range of-7.33% and 6.26%. Our results support that central composite design can be used to optimize drug release from HPMC/pectin/calcium matrix tablet with high predictability.
基金Supported by an unrestricted grant From the Hong Kong Society of Digestive Endoscopy and the Natural Science Foundation of Guangdong Province of China(No.010713)
文摘AIM: Mechanisms underlying the chemopreventive effects of cyclooxygenase (COX) inhibitors remain elusive. We have previously shown that celecoxib but not indomethacin could prevent carcinogen-induced gastric cancer development in Wistar rats. This chemopreventive effect appeared to be independent of COX-2 and prostaglandin (PG) E2 suppression since the lowest PGE2 was obtained in indomethacin group.This study compared the cell kinetic changes in stomachs of rats after treatment with celecoxib (5, 10, 20 mg/(kg·d)) or indomethacin (3 mg/(kg·d)) to gain more insights into the chemopreventive mechanism.METHODS: The apoptosis and proliferation indexes in gastric tumor, adjacent non-cancer tissues and normal gastric tissues were determined. Apoptosis was quantified by apoptotic nuclei counting and TUNEL, whereas proliferation was determined by Ki67 immunostaining.RESULTS: Treatment with either celecoxib or indomethacin inhibited gastric tumor proliferation by more than 65% (P＜0.02). However, celecoxib caused a dose-dependent increase in apoptosis (P＜0.05) which was not seen in indomethacin-treated tumors (P = 0.54). The highest apoptosis to proliferation ratio was seen in tumors treated with celecoxib at 10 mg/(kg·d). Treatment with this dose of celecoxib was associated with the lowest incidence of gastric cancer development.CONCLUSION: Our findings suggest that the difference in chemopreventive effects of indomethacin and celecoxib in this animal model of gastric carcinogenesis is largely due to the differential cell kinetic changes, which does not correlate with the degree of COX-2 and PG suppression.
基金Supported by TáMOP-4.2.2.A-11/1/KONV-2012-0035 and OTKA K101521
文摘AIM: To investigate the effectiveness of rectally administered indomethacin in the prophylaxis of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis and hyperamylasaemia in a multicentre study.
基金Supported by National Natural Science Foundation of China, No. 30271516
文摘AIM: It has been reported that regular consumption of nonsteroidal anti-inflammatory drugs like indomethacin decreases the incidence and mortality rate of a number of gastrointestinal cancers. We aimed to explore the efficacy and possible mechanisms of indomethacin on tumor growth and tumor angiogenesis of human colon cancer xenografts in nude mice. METHODS: MTT (thiazolyl blue) assay was used to assess the effect of indomethacin on cultured human colorectal cancer cell line HCT116. HCT116 cells were inoculated subcutaneously into BALB/c-nu/nu mice. After oral administration of indomethacin, 3 mg/kg·d for 4 wk, animals were sacrificed by cervical dislocation. Immunohistochemical staining was employed to determine the microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression in tumor tissues. RESULTS: Indomethacin, a non-selective COX inhibitor, significantly decreased the viability of HCT116 cells in a dose-dependent manner (P<0.05) with 50% inhibition at approximately 318.2±12.7 μmol/L Growth of HCT116 cell tumor was significantly suppressed by indomethacin. The tumor volume was significantly decreased in the treated group (458.89±32.07 mm3) compared to the control group (828.21±31.59 mm3) (P<0.05). The MVD of the treated group (19.50±5.32) was markedly decreased compared to the control group (37.40±4.93) (P<0.001). The VEGF expression of the treated group (1.19±0.17) was obviously reduced as compared to the control group (1.90±0.48) (P<0.01). The decrease in MVD was positively correlated with the decrease of VEGF expression (rs = 0.714, P<0.05). We did not see gastrointestinal complications in the treated group and no differences were noted in the body weight of the mice between the two groups throughout the study CONCLUSION: Indomethacin can significantly decrease the viability of cultured HCT116 cells and retard human colorectal HCT116 cell tumor growth via inhibiting tumor angiogenesis, which might be through reduction of VEGF expression.
文摘OBJECTIVE： Carica papaya is an important fruit with its seeds used in the treatment of ulcer in Nigeria This study investigated the anti-ulcerogenic and antioxidant activities of aqueous extract of Carica papaya seed against indomethacin-induced peptic ulcer in male rats. METHODS： Thirty male rats were separated into 6 groups （A-F） of five rats each. For 14 d before ulcer induction with indomethacin, groups received once daily oral doses of vehicle （distilled water）, cimetidine 200 mg/kg body weight （BW）, or aqueous extract of C. papaya seed at doses of 100, 150 or 200 mg/kg BW （groups A, B, C, D, E and F, respectively）. Twenty-four hours after the last treatment, groups B, C, D, E and F were treated with 100 mg/kg BW of indomethacin to induce ulcer formation. RESULTS： Carica papaya seed extract significantly （P〈0.05） increased gastric pH and percentage of ulcer inhibition relative to indomethacin-induced ulcer rats. The extract significantly （P〈0.05） decreased gastric acidity, gastric acid output, gastric pepsin secretion, ulcer index and gastric secretion volume relative to group B. These results were similar to that achieved by pretreatment with cimetidine. Specific activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase in the extract-treated groups （D, E and F） were increased significantly over the group B （P〈0.05）. Pretreatment with the seed extract protected rats from the indomethacin-mediated decrease in enzyme function experienced by the group B. Similarly, indomethacin-mediated decrease in reduced glutathione level and indomethacin-mediated increase in malondialdehyde were reversed by Carica papaya extract. CONCLUSION： In this study, pretreatment with aqueous extract of Carica papaya seed exhibited anti- ulcerogenic and antioxidant effects, which may be due to the enhanced antioxidant enzymes.
基金supported by the Pharmacology Laboratory of Qingdao Universityfunding from the Dalian Bangchui Island Seafood Co., Ltd.+3 种基金Shandong Medical and Health Science and Technology Development Plan (No. 2013WS0270)Natural and Science Funding of Shandong Province (ZR2014HM094)College and University Scientific Research Development Program of Shandong Province (J15LL5T)Qingdao People's Livelihood Science and Technology Plan (14-2-3-8-nsh)
文摘Our study aimed to investigate the protective effects of Holothurian intestines(HI) on NSAIDs-induced gastric mucosal damage and the possible mechanism. At first, 60 male Wistar rats were induced of gastric lesions with indomethacin(IDM, 30 mg kg^(-1)). The rats were pretreated for 15 consecutive days with saline, sucralfate, or HI(0.4g kg^(-1) d-1, 0.8 g kg^(-1) d^(-1) and 1.6 g kg^(-1) d^(-1)) prior to IDM treatment, followed by evaluations of macroscopic damage and microscopic features; and investigation of the levels of inflammatory cytokines, oxidative stress parameters, gastric mucosal prostaglandin E2(PGE2) and total hexosamine in tissues. The expression of COX-1 and COX-2 m RNA in the gastric tissue were determined by quantitative polymerase chain reaction(q PCR). Pathological gastric ulcer indexes, levels of pro-inflammatory cytokines(IL-1β, IL-17, TNF-α) and lipid peroxidation were significantly decreased in HI-treated groups, whereas the levels of protective factors(TGF-β, GSH, SOD activity and PGE2) were significantly elevated especially in the group with HI 1.61 g kg^(-1) d^(-1)(P < 0.05). Furthermore, the expression of COX-2 mRNA decreased significantly in HI groups(P < 0.05). The study investigates that holothurian intestines may act as a kind of marine medicine which have protective effect on IDM-induced gastric ulcer, which could be a dietary preventive agent for the prevention of gastric damage.
文摘AIM： To investigate the mucosal protective effect and the mechanisms of action of the anti-ulcer drug irsogladine maleate in gastric injury induced by indomethacin in rats. METHODS： Gastric mucosal injury was induced in male Hos：Donryu rats by oral administration of indomethacin at a dose of 48 mg/kg. One hour before indomethacin treatment, animals were orally pretreated with irsogladine maleate at doses of 1 mg/kg, 3 mg/kg or 10 mg/kg. Four hours after indomethacin administration, the animals were sacrificed and their stomachs were rapidly removed and processed for the evaluation of gastric mucosal damage and the determination of the concentrations of tumor necrosis factor-α （TNF-α）, interleukin-1β （IL-1β）, IL-8 and myeloperoxidase （MPO） in mucosal tissues. RESULTS： Linear hemorrhagic mucosal lesions were observed primarily in the glandular stomach 4 h alter oral administration of indomethacin. Pretreatment with irsogladine maleate markedly reduced the number and severity of these lesions in a dose-dependent manner. The mucosal concentrations of proinflammatory cytokines （TNF-α, IL-1β, and IL-8） and MPO, which indicates the degree of mucosal infiltration by neutrophils, increased concomitantly with the occurrence of gastric injury in the indomethacintreated rats. Pretreatment with irsogladine maleate significantly decreased the levels of these inflammatory factors in gastric tissue elicited by indomethacin.CONCLUSION： The mucosal protective effects afforded by irsogladine maleate on gastric injury induced by indomethacin are mediated by inhibition of mucosal proinflammatory cytokine production and neutrophil infiltration, leading to suppression of mucosal inflammation and subsequent tissue destruction.
文摘Objective:To investigate the restorative effect of Pterocarpus erinaceus(P.erinaceus) and homopterocarpin.an isoflavonoid isolated from it.on indomethacin-indueed disruption in gastric homeostasis in rats.Methods:Adult rats were dn ided into five groups and lasted for 48 h before treatment.Group I received olive oil(vehicle),group 2 received 25 ing/kg indomethaein while groups 3-5 received cimetidine(100 mg/kg).lioniopterocarpin(25 mg/kg) and P.erinaceus ethanolie stem hark extract(100 mg/kg) respectively.After 1 h.all the groups except group 2 were administered 25 mg/kg of indomethacin.One hour later,the rats were sacrificed and the ulcer index and other gaslroprotective indices were evaluated.Results:Indomethacin caused significant injury to the stomach of the rats as reflected in the ulcer indices(9.0±1.4) as compared with that of control(2.0±0.0).Equally,there were significant increases in gastric acid concentration and malondialdehvde level in the stomachs of the ulcerated animals compared with the control.However mucus content,reduced gluthatione level and gastric pH were significantly reduced in the ulcerated animals compared with the control.Pretreatment with either Pterocarpus bark extract or homopterocarpin reversed the effects of indomethaein on the evaluated parameters.Conclusions:These results indicate that both homopterocarpin and Plerocarpus extract offered gastroprotection against indomethacin-induced ulcer by antioxidative mechanism and the modulation of gastric homeostasis.The results also suggest that homopterocarpin might he responsible for.or contribute to the antiulcerogenic property of P.erinaceus.
基金Liliana Zazueta-Beltran,Lorena Medina-Aymerich and Nadia Estela Diaz-Triste were supported by CONACYT fellowships
文摘OBJECTIVE： To determine the role of a pharmacokinetic interaction in the protective effect of curcumin against the gastric damage induced by indomethacin administration as such or as its prodrug acemetacin. METHODS： Wistar rats orally received single dose of indomethacin （30 mg/kg） with and without curcumin （30 mg/kg）; gastric injury was evaluated by determining the total damaged area. Additional groups of rats received an oral single dose of indomethacin （30 mg/kg） or its prodrug acemetacin （34.86 mg/kg） in the presence or absence of curcumin （30 mg/kg）. Indomethacin and acemetacin concentrations in plasma from blood draws were determined by high-performance liquid chromatography Plasma concentration-against-time curves were constructed, and bioavailability parameters, maximal concentration （Cmax） and area under the curve to the last sampling time （AUC0_t） were estimated. RESULTS： Concomitant administration of indomethacin and curcumin resulted in a significantly reduced gastric damage compared to indomethacin alone. However, co-administration of curcumin did not produce any significant alteration in the bioavailability parameters of indomethacin and acemetacin after administration of either the active compound or the prodrug. CONCLUSION： Curcumin exhibits a protective effect against indomethacin-induced gastric damage, but does not produce a reduction of the bioavailability of this nonsteroidal anti-inflammatory drug, indomethacin. Data thus suggest that a pharmacokinetic mechanism of action is not involved in curcumin gastroprotection.
文摘KangFuXinYe(KFX),the ethanol extract of the dried whole body of Periplaneta americana,is a well-known important Chinese medicine preparation that has been used to treat digestive diseases such as gastric ulcers for many years in China.However,its therapeutic effect and mechanism are not yet well understood.Thus,the aim of this study was to investigate the gastroprotective effects of KangFuXinYe(KFX)in indomethacin-induced gastric damage.Rats were randomly divided into six groups as follows:control,treated with indomethacin(35 mg·kg^-1),different dosages of KFX(2.57,5.14 and 10.28 mL·kg^-1,respectively)plus indomethacin,and sucralfate(1.71 mL·kg^-1)plus indomethacin.After treatment,rat serum,stomach and gastric homogenates were collected for biochemical tests and examination of histopathology firstly.Rat serum was further used for metabolomics analysis to research possible mechanisms.Our results showed that KFX treatment alleviated indomethacin-induced histopathologic damage in rat gastric mucosa.Meanwhile,its treatment significantly increased cyclooxygenase-1(COX-1),prostaglandin E2(PGE2)and epidermal growth factor(EGF)levels in rat serum and gastric mucosa.Moreover,KFX decreased cyclooxygenase-2(COX-2)and interleukin-6(IL-6)levels.Nine metabolites were identified which intensities significantly changed in gastric damage rats,including 5-hydroxyindoleacetic acid,indoxylsulfuric acid,indolelactic acid,4-hydroxyindole,pantothenic acid,isobutyryl carnitine,3-methyl-2-oxovaleric acid,sphingosine 1-phosphate,and indometacin.These metabolic deviations came to closer to normal levels after KFX intervention.The results indicate that KFX(10.28 mL·kg^-1)exerts protective effects on indomethacin-induced gastric damage by possible mechanisms of action(regulating tryptophan metabolism,protecting the mitochondria,and adjusting lipid metabolism,and reducing excessive indomethacin).
文摘AIM: To study the effects of indomethacin on the isolated transverse and longitudinal rat gastric fundus strips.METHODS: The strips were suspended in an organ bath containing oxygenated Krebs solution, and contractile responses to electrical field stimulation were recorded on a physiograph in an isotonic manner after administration of cumulative concentrations of indomethacin. The effects of indomethacin on the strips pretreated with KATP channel modulators, diazoxide and glybenclamide were studied.RESULTS: Treatment of the transverse strips with indomethacin resulted in a concentration-dependent inhibitory response. In longitudinal strips, biphasic responses were seen, which included a stimulatory response at low concentrations of indomethacin, followed by an inhibitory response at higher concentrations.Diazoxide pre-treatment inhibited the stimulatory response of longitudinal strips. Glybenclamide pre-treatment not only blocked inhibitory effect of the low concentrations of indomethacin on transverse strips, but also increased the amplitude of contractions. Moreover, the drug decreased the amplitude of contractions in longitudinal strips.CONCLUSION: Responses of the isolated longitudinal and transverse rat gastric fundus strips to indomethacin are not similar, and are influenced by KATP channel modulators.
基金Supported by the National Science Council of Taiwan (grant no. NSC 92-2314-B-075-036) Taipei Veterans General Hospital (VGH-93-212)
文摘AIM: Vasodilatation and increased capillary permeability have been proposed to be involved in the pathogenesis of acute and chronic form of hepatic encephalopathy. Prostacyclin (PGI2) and nitric oxide (NO) are important contributors to hyperdynamic circulation in portal hypertensive states. Our previous study showed that chronic inhibition of NO had detrimental effects on the severity of encephalopathy in thioacetamide (TAA)-treated rats due to aggravation of liver damage. To date, there are no detailed data concerning the effects of PGI2 inhibition on the severity of hepatic encephalopathy during fulminant hepatic failure. METHODS: Male Sprague-Dawley rats weighing 300-350 g were used. Fulminant hepatic failure was induced by intraperitoneal injection of TAA (350 mg/(kg·d) for 3 d. Rats were divided into two groups to receive intraperitoneal injection of indomethacin (5 mg/(kg·d), n = 20) or normal saline (N/S, n = 20) for 5 d, starting 2 d before TAA administration. Severity of encephalopathy was assessed by the counts of motor activity measured with Opto-Varimex animal activity meter. Plasma tumor necrosis factor-α (TNF-α, an index of liver injury) and 6-keto-PGF1α (a metabolite of PGI2) levels were measured by enzyme-linked immunosorbent assay. RESULTS: As compared with N/S-treated rats, the mortality rate was significantly higher in rats receiving indomethacin (20% vs5%, P<0.01). Inhibition of PGI2 created detrimental effects on total movement counts (indomethacin vs N/S: 438±102 vs 841±145 counts/30 min, P<0.05). Rats treated with indomethacin had significant higher plasma levels of TNPa (indomethacin vs N/S: 22±5 vs 10±1 pg/mL, P<0.05) and lower plasma levels of 6-keto-PGF1α (P<0.001), but not total bilirubin or creatinine (P>0.05), as compared with rats treated with N/S. CONCLUSION: Chronic indomethacin administration has detrimental effects on the severity of encephalopathy in TAA-treated rats and this phenomenon may be attributed to the aggravation of liver injury. This study suggests that PGI2 may provide a protective role in the development of fulminant hepatic failure.
基金Supported by 90th Anniversary Fund of Chulalongkorn University(Ratchada phiseksomphot Endowment Fund)The Grant of Ratchadaphiseksomphot,Faculty of Medicine,Chulalongkorn University,Bangkok,Thailand
文摘AIM: To evaluate the protective effects of Aloe vera on gastric injury in rats with indomethacin (IMN)-induced gastropathy.
基金This work was supported by National Basic Research Program of China(973 Program)(2009CB930300)National Natural Science Foundation of China(81072605)Shenyang Special Fund for Exploration of Intellectual Resources.
文摘We applied a combination of inorganic mesoporous silica material,frequently used as drug carriers,and a natural organic polymer alginate(ALG),to establish a sustained drug delivery system for the poorly water-soluble drug Indomethacin(IND).Mesoporous silica nanospheres(MSNs)were synthesized using an organic template method and then functionalized with aminopropyl groups through postsynthesis.After drug loading into the pores of aninopropyl functionalized MSNs(AP-MSNs),IND loaded AP-MSNs(IND-AP-MSNs)were encapsulated by ALG through the ionic interaction.The effects of surface chemical groups and ALG layer on IND release were systematically studied using scanning electron microscopy(SEM),transmission electron microscopy(TEM),nitrogen adsorption,zetapotential analysis and TGA analysis.The surface structure and surface charge changes of the ALG encapsulated AP-MSNs(ALG-AP-MSNs)were also investigated.The results showed that sustained release of IND from the designed drug delivery system was mainly due to the blockage effect from the coated ALG.We believe that this combination will help designing oral sustained drug delivery systems for poorly water-soluble drugs.
基金This project was supported by a grant from Hubei Science and Technology Com mittee(No.96 1P190 1)
文摘Effects of two types of intrauterine device (IUD) on the prostaglandins and endothelin (ET) in uterus and on the endometrial morphology in rats and rabbits, and Cu 2+ releasing amounts of both IUDs in vitro were observed. The results showed that the inhibiting action of the indomethacin releasing copper IUD (FICu IUD) on the PGI 2 was stronger than that on the TXA 2, the ratio of 6 keto PGF 1α /TXB 2 was reduced with the increase of the doses. There were significant differences between the groups. The FICu IUD could inhibit the rising of the ET level and lighten the endometrial impairment caused by the FCu IUD, and promote copper ion release. It was suggested that indomethacin released by FICu IUD could effectively reduce abnormal uterine bleeding.
文摘Topical administration is the most common and acceptable use for the treatment of ocular disease.However,the major problem of ocular drug delivery is the rapid drug elimination from the pre-ocular area leading to poor ocular bioavailability[1].Nanostructure lipid carriers(NLC)possess a significant enhancement in ocular bioavailability by increasing the permeability and mucoadhesive property[2].In this study,indomethacin(IND),non-steroidal anti-inflammatory,was used as a model drug[3].
基金Supported by the National Natural Science Foundation of China, No. 30271516
文摘AIM: To establish the two-dimensional gel electrophoresis (2-DE) profiles of indomethacin (IN)-treated human colon cancer cell line HCT116, and to provide a new way to study its anti-tumor molecular mechanism through analyzing a variety of protein maps.METHODS: Two-DE profiles of HCT116 were established in IN-treated and untreated groups. Total proteins were separated by immobilized pH gradient-based 2-DE. The gels were stained by silver, scanned by ImageScanner,and analyzed with Image Master software.RESULTS: Clear background, well-resolved and reproducible 2-DE patterns of HCT116 cells were acquired in IN-treated and untreated group. The average deviation of spot position was 0.896±0.177 mm in IEF direction and 1.106±0.289 mm in SDS-PAGE direction respectively. In IN-treated group,1 169±36 spots were detected and 1 061±32 spots were matched, the average matching rate was 90.6% in three gels. In untreated group, 1 256±50 spots were detected and 1 168±46 spots were matched, the average matching rate was 93.0% in three gels. Forty-five differential protein spots were displayed between IN-treated and untreated groups. Of which, 34 protein spots decreased and 9showed higher expression in IN-treated group, and only two protein spots showed an expression in untreated cells.CONCLUSION: Two-DE profiles of IN-treated and untreated HCT116 cells were established. Apparent 45 different protein spots were detected in IN-treated and untreated HCT116 cells. The analysis on differential protein spots may serve as a new way to study the molecule mechanism of IN-treated colon cancer.
基金supported by the National Key Technology R&D Program of China(No.2011BAI10B07)the National Basic Research Program(973)of China(No.2012CB517603)the National High-Tech R&D Program(863)of China(No.2012AA02A512)
文摘Objective： To evaluate the renoprotection effects of non-steroidal anti-inflammatory drugs （NSAIDs） in renal ischemia-reperfusion injury （IRI） and the cyclooxygenase （COX）-1/2 blockade association by indomethacin （IMT） in the mice model. Methods： After the left renal pedicle of mice was clamped, IMT was administrated by intraperitoneal injection with four doses： 1, 3, 5, and 7 mg/kg. Blood and kidney samples were collected 24 h after IRI. The renal functions were assayed by the cytokines and serum creatinine （SCr） using enzyme-linked immunosorbent assay （ELISA） kits. Kidney samples were analyzed by hematoxylin and eosin （H＆E） and immunohistochemistry stainings. Results： The mice administered with 5 mg/kg IMT had a marked reduction in SCr and significantly less tubular damage The tumor necrosis factor a （TNF-α） activity in renal homogenates and interleukin 6 （IL-6） activity in serum had a marked reduction at doses of 5 and 7 mg/kg IMT. The administration of 3 and 5 mg/kg IMT had a marked reduction in the ratio of thromboxane B2 to 6-keto-prostaglandin F1α. COX-1 and COX-2 stainings were weaker in 5 mg/kg IMT groups than that in the other groups. Conclusions： There was a dose response in the IMT function of renal IRI in mice, and IMT had a protective effect in a certain dose range. The effect of IMT on mice IRI was related to COX-1/2 blockades.
