Effects Of Etodolac Research Articles

Effects of paracetamol and etodolac on plasma adrenaline levels of rats

Adrenaline, which is released from the adrenal medulla, is an important compound in the reaction of sympathetic nerve system. This hormone can increase the body’s normal metabolic rate up to 100 %, and thus improves the effectiveness of the whole body. It has been considered to be involved in the control of inflammation. Therefore, we investigated whether there are effects of paracetamol and etodolac on adrenaline levels of rats after oral administration. The rats were divided into three subgroups while analysing the effects of adrenaline on paracetamol and etodolac. The first group was the control, second group was composed of rats given paracetamol, and third group was composed of rats given etodolac. In order to measure adrenaline plasma concentration, we have used the high-performance liquid chromatography coupled with fluorescence detection. According to the result of the analysis, there are statistically important differences at adrenaline levels between control group and rats-applied drugs. Obtained results showed that although adrenaline level in the paracetamol-applied group decreased, adrenaline level in the etodolac-applied group increased. It is concluded that different effects of etodolac and paracetamol on circulating adrenaline levels can be related to their different effects on inflammation, COX enzymes, prostaglandins, etc. Also we can suggest usage of paracetamol instead of etodolac in patients with cardiovascular system diseases.

Etodolac, a racemic nonsteroidal anti‐inflammatory drug, exhibits low gastrointestinal toxicity: relation to the effects of the enantiomers (840.13)

Etodolac, a racemic (LR) nonsteroidal anti‐inflammatory drug (NSAID), has higher gastric safety compared to other conventional NSAIDs. However, it remains unknown whether the LR etodolac shows less adverse action in the small intestine. In the present study, we examined the effect of etodolac, both L/R and the enantiomers (S and R) on the gastric and small intestinal mucosa. Methods: Male SD rats were used. Etodolac (5‐50 mg/kg), both LR, S and R, was given p.o. in 18 h‐fasted or non‐fasted rats, and the stomach or the small intestine was examined for lesions 4 or 24 h later, respectively. Results: LR‐etodolac and S‐etodolac dose‐dependently caused lesions in both the stomach and small intestine, yet the effect of the former was much less potent compared to the latter. R‐etodolac did not cause damage even at 50 mg/kg. On the other hand, pretreatment with R‐etodolac dose‐dependently prevented the development of gastric lesions induced by indomethacin. The mucosal PGE2 content in the stomach and small intestine was significantly decreased by both LR‐etodolac and S‐etodolac, but not R‐etodolac. Conclusion: These results suggest that LR‐etodolac has less ulcerogenic properties in the gastrointestinal mucosa and showed that this safety profile of LR‐etodolac may be explained by the mucosal protective action of R‐etodolac.

Etodolac Blocks the Allyl Isothiocyanate-Induced Response in Mouse Sensory Neurons by Selective TRPA1 Activation

Background and Purpose: The excitability of nociceptors is modulated by the transient receptor potential cation channel, ankyrin subfamily, member 1 (TRPA1). We have previously reported that etodolac, a nonsteroidal anti-inflammatory drug, attenuates mechanical allodynia in a mouse model of neuropathic pain by a mechanism that is independent of cyclooxygenase inhibition. Here, we investigate the role of TRPA1 in the mechanism of the antinociceptive action of etodolac in vitro and in vivo. Experimental Approach: Ca²⁺ influx was measured in HEK-293 cells expressing mouse TRPA1 and in mouse dorsal root ganglion (DRG) neurons. The effect of etodolac on the nociceptive behavior induced in mice by the TRPA1 agonist allyl isothiocyanate (AITC) was also measured. Results: Etodolac induced Ca²⁺ influx in HEK-293 cells expressing mouse TRPA1 and in mouse DRG neurons. The Ca²⁺ influx induced by etodolac was inhibited by pretreatment with the TRPA1-specific antagonist HC-030031. In contrast, etodolac did not induce Ca²⁺ influx in cells expressing TRPV1, TRPV2 or TRPM8. In addition, pretreatment with etodolac inhibited the Ca²⁺ influx induced by AITC. Conclusion and Implication: Etodolac showed a selective TRPA1 agonist action, providing evidence that etodolac desensitizes nociceptors by the selective activation of TRPA1. Etodolac may be clinically useful in the treatment of neuropathic pain.

PGE2 facilitates the activation of renal sensory nerves by a positive feedback mechanism involving activation of PLC and COX‐2

PGE2 facilitates the activation of sensory nerves. In the kidney, norepinephrine (NE)‐mediated activation of α1‐adrenoceptors activates PLC and increases PGE2 synthesis. PGE2 activates adenylyl cyclase(AC)/cAMP/PKA leading to release of substance P and stimulation of renal sensory nerves. NE‐mediated activation of renal α2‐adrenoceptors suppresses the activation of renal sensory nerves by decreasing the activation of AC and PG synthesis. Activation of AC by forskolin enhanced NE‐induced PGE2 synthesis and substance P release. Because these studies suggest that PGE2 may increase PGE2 synthesis by activating AC, we studied if inhibition of PG‐synthesis would reduce the release of substance P produced by PGE2. In isolated rat renal pelvises, PGE2, 0.03 μM, increased substance P release from 4.5±0.3 to 11.5±0.6 pg/min. Indomethacin or the COX‐2 inhibitors etodolac or DFU reduced the PGE2‐induced release of substance P by 34±5% and 29±3%, the effects of etodolac and DFU being similar. The PGE2‐induced release of substance P was reduced by the PLC inhibitor U73122 by 62±13% and the PKC inhibitor calphostine by 49±7%. In indomethacin‐treated pelvises, U73122 failed to reduce the PGE2‐induced release of substance P. We conclude that PGE2 facilitates the activation of renal sensory nerves by a positive feedback mechanism involving activation of AC activating PLC leading to induction of COX‐2 and PGE2 release.

Effects of Etodolac on P450 Isoform-specific Activities in Human Hepatic Microsomes

The effects of etodolac (CAS 41340-25-4) on P450 isoform-specific activities in human hepatic microsomes were examined. Etodolac had little effect on 7-ethoxyresorufin O-deethylation (CYP1A2), coumarin hydroxylation (CYP2A6), 7-benzyloxyresorufin O-debenzylation (CYP2B6), S-mephenytoin hydroxylation (CYP2C19), bufuralol hydroxylation (CYP2D6), chlorzoxazone hydroxylation (CYP2E1) and nifedipine oxidation (CYP3A4) at concentrations ranging from 10 to 50 micromol/L. Etodolac inhibited tolbutamide hydroxylation (CYP2C9) with the Ki value of 64 micromol/L, suggesting that it is a weak inhibitor of CYP2C9. The in vivo drug interaction was predicted from the in vitro data using the [I]/([I] + Ki) value. Because the value was calculated to be almost 1, it is not likely that etodolac causes the drug interactions with the CYP2C9 substrates.

Etodolac Attenuates Hippocampal Blood Flow Responses Induced by Tooth Pulp Stimulation in Rats

In this study, we investigated whether increases in hippocampal blood flow (HBF) by tooth pulp stimulation (TPS) are mediated via the activation of cyclooxygenase-2 (COX-2). We measured mean arterial blood pressure (MABP) and HBF in urethane-anesthetized rats using laser Doppler flowmetry and examined the effects of etodolac, a specific COX-2 inhibitor, on TPS-induced MABP and HBF responses. The MABP response was not attenuated by the intraperitoneal (i.p.) administration of etodolac (10 mg/kg); however, the HBF response was significantly attenuated by etodolac administration. These results suggest that COX-2 may be involved in the mechanisms regulating TPS-induced HBF responses.

Administration of the selective cyclooxygenase (COX)-2 inhibitor etodolac prolongs cardiac allograft survival in a mouse model

Etodolac, a selective cyclooxygenase-2 (COX-2) inhibitor, is a non-steroidal anti-inflammatory drug. COX-2 is a key factor in the progression of inflammation. Although inflammation is an essential pathologic feature of cardiac allograft rejection, the role of COX-2 in this process remains unclear. The aim of this study was to investigate the expression of COX and the effects of etodolac in a mouse cardiac allograft model. Balb/c mice (H-2d) were used as recipients and C57BL/6 (H-2b) mice as heart donors. Heart function was evaluated daily after transplantation by regular abdominal palpation of the heart and by laparotomy in cases where the beating became weak. Rejection was defined as total cessation of cardiac muscle contraction. COX-2 expression was analyzed by immunohistochemistry. Cardiac isograft was well tolerated (>150 days, n=5), while non-treated cardiac allograft was rapidly rejected (mean10.9±2.4, n=7). In the etodolac-treated cardiac allograft (10 mg/kg/day by hypodermic injection), survival was extended to 18.53±2.1 days (n=7). The necrotic area and the grade of COX-2 immunostaining were more significantly reduced in the etodolac-treated cardiac allograft than in the non-treated cardiac allograft at day14. These results indicate that etodolac contributes to protection against rejection after heart transplantation. Etodolac could therefore be used to suppress graft rejection by means of its anti-inflammatory properties.

M1737 R-Etodolac Induces E-Cadherin and Suppresses Colitis-Related Mouse Colon Carcinogenesis

Background: Colorectal cancer is one of the most serious complications of ulcerative colitis (UC) and the risk of UC-associated neoplasia increases as the region and duration of the disease increase. As we have shown previously, the selective cyclooxygenase (COX)-2 inhibitor is effective in diminishing carcinogenesis in an murine model of UC (DDW 2006).1 However, this might exacerbate dextran sulfate sodium (DSS) colitis in mice. The selective COX-2 inhibitor Etodolac is marketed as a racemic mixture of the Rand Senantiomers that are not metabolically interconvertible. The biochemical and pharmacological effects of Etodolac are due to the S-enantiomer, while R-enantiomer lacks COX-inhibitory activity. Therefore, R-Etodolac has potential advantage of avoiding COX-2 inhibitory adverse effects. In this study, we evaluated the effect of R-Etodolac on colitis-related mouse colon carcinogenesis. Methods: The mice received 1,2-dimethlhydrazine (DMH) at a dose of 20mg/kg body wt subcutaneously three times within 1 week of reaching 6 weeks of age. Starting 1 week after the DMH injection, chronic colitis was induced in mice by administration of 2 cycles of DSS (each cycle: 3% DSS for 7 days and then distilled water for 14 days). The mice were killed 28 days after the completion of the 2 cycles. The mice were divided into the following groups: group A served as a disease control; group B received low (2mg/kg) dose of REtodolac every 3 days by oral gavage during the whole period; group C received high (10mg/ kg) dose of R-Etodolac every 3 days by oral gavage during the whole period; group D received no agents including DSS and served as a normal control. Results: The administration of R-Etodolac decreased the disease activity index during the administration cycle of DSS. The mean number of tumors was 17.8 in group A, 15.2 in group B and 6.0 in group C. In group C, R-Etodolac significantly suppressed the occurrence of neoplasia (p<0.05). Strong COX-2 expression was detected by immunohistochemistry in the neoplastic lesions while E-cadherin expression was not observed. Although treatment of R-Etodolac unaffected to the COX-2 expression, it was found that R-Etodolac significantly enhanced the expression of E-cadherin in the neoplastic lesions and background mucosa (i.e. lesion-free colon). Conclusion: The administration of R-Etodolac exerts a suppressive effect on the development of neoplasia in a murine model of DSS induced colitis without exacerbation of the colitis. These results suggest that R-Etodolac could be useful in the prevention of UC-associated neoplasia. 1. Inoue T et al. J Gastroenterol Hepatol 2009; 22: 1474-81.

M1738 The Genetically Modified Lactococcus Lactis Ova Modulates T-Cells Through an Antigen-Specific Effect on Dendritic Cells

Background: Colorectal cancer is one of the most serious complications of ulcerative colitis (UC) and the risk of UC-associated neoplasia increases as the region and duration of the disease increase. As we have shown previously, the selective cyclooxygenase (COX)-2 inhibitor is effective in diminishing carcinogenesis in an murine model of UC (DDW 2006).1 However, this might exacerbate dextran sulfate sodium (DSS) colitis in mice. The selective COX-2 inhibitor Etodolac is marketed as a racemic mixture of the Rand Senantiomers that are not metabolically interconvertible. The biochemical and pharmacological effects of Etodolac are due to the S-enantiomer, while R-enantiomer lacks COX-inhibitory activity. Therefore, R-Etodolac has potential advantage of avoiding COX-2 inhibitory adverse effects. In this study, we evaluated the effect of R-Etodolac on colitis-related mouse colon carcinogenesis. Methods: The mice received 1,2-dimethlhydrazine (DMH) at a dose of 20mg/kg body wt subcutaneously three times within 1 week of reaching 6 weeks of age. Starting 1 week after the DMH injection, chronic colitis was induced in mice by administration of 2 cycles of DSS (each cycle: 3% DSS for 7 days and then distilled water for 14 days). The mice were killed 28 days after the completion of the 2 cycles. The mice were divided into the following groups: group A served as a disease control; group B received low (2mg/kg) dose of REtodolac every 3 days by oral gavage during the whole period; group C received high (10mg/ kg) dose of R-Etodolac every 3 days by oral gavage during the whole period; group D received no agents including DSS and served as a normal control. Results: The administration of R-Etodolac decreased the disease activity index during the administration cycle of DSS. The mean number of tumors was 17.8 in group A, 15.2 in group B and 6.0 in group C. In group C, R-Etodolac significantly suppressed the occurrence of neoplasia (p<0.05). Strong COX-2 expression was detected by immunohistochemistry in the neoplastic lesions while E-cadherin expression was not observed. Although treatment of R-Etodolac unaffected to the COX-2 expression, it was found that R-Etodolac significantly enhanced the expression of E-cadherin in the neoplastic lesions and background mucosa (i.e. lesion-free colon). Conclusion: The administration of R-Etodolac exerts a suppressive effect on the development of neoplasia in a murine model of DSS induced colitis without exacerbation of the colitis. These results suggest that R-Etodolac could be useful in the prevention of UC-associated neoplasia. 1. Inoue T et al. J Gastroenterol Hepatol 2009; 22: 1474-81.

Profiling of cell cycle genes of breast cells exposed to etodolac

Breast cancer represents the second leading cause of cancer-related deaths in the world. There is increasing evidence that perturbation of cell cycle regulation is an important contributing factor to various cancer progression stages. There are key checkpoints in the cell cycle involving various regulatory proteins. The relationship between these cell cycle regulatory proteins and cell cycle arrest by cyclo-oxygenase (COX) inhibitors during neoplastic progression remains largely unknown. Preclinical studies and epidemiological investigations have consistently shown that non-steroidal anti-inflammatory drugs have some anti-proliferative and anti-oxidative stress response on various tumors. In this study, the effect of etodolac, a 1,8-diethyl-1,3,4,9-tetrahydro-pyrano (3,4-beta) indole-1-acetic acid on signaling pathways was investigated by examining the differential expression of various cell cycle regulatory protein genes. A human cell cycle gene array was used to profile the expression of 96 genes involved in the cell cycle regulation. Differentially expressed genes were highly altered by etodolac treatment. Twenty-six genes were up- and 20 down-regulated with 0.5 and 2 mM etodolac treatment, respectively. Seven genes (ATM, BAX, CCNA2, CDC27, RAD50 and p21) were prominently altered, and six (ATM, CCND2, CCNF, CDC20, CDK1A and RAD50) were commonly altered with both concentrations. This finding indicated that etodolac could play a critical role on cancer cells by inducing cell death.

Role of COX-2 in cough reflex sensitivity to inhaled capsaicin in patients with sinobronchial syndrome

BackgroundSinobronchial syndrome is a cause of chronic productive cough. Inflammatory mediators are involved in the pathophysiology of chronic productive cough. Accumulating evidences indicate that cyclooxygenase (COX)-2, one of the inducible isoforms of COX, is a key element in the pathophysiological process of a number of inflammatory disorders. However, little is known about the role of COX-2 in chronic productive cough in patients with sinobronchial syndrome known as neutrophilic bronchial inflammation.MethodsThe effect of etodolac, a potent COX-2 inhibitor, on cough response to inhaled capsaicin was examined in 15 patients with sinobronchial syndrome in a randomized, placebo-controlled cross-over study. Capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of airway cough reflex sensitivity.ResultsThe cough threshold was significantly (p < 0.03) increased after two-week treatment with etodolac (200 mg twice a day orally) compared with placebo [37.5 (GSEM 1.3) vs. 27.2 (GSEM 1.3) μM].ConclusionsThese findings indicate that COX-2 may be a possible modulator augmenting airway cough reflex sensitivity in patients with sinobronchial syndrome.

The Effects of Etodolac, Nimesulid and Naproxen Sodium on the Frequency of Sister Chromatid Exchange after Enclused Third Molars Surgery

PurposeNon-steroidal anti-inflammatory drugs (NSAID) are frequently used in oral surgical procedures in dentistry. The evaluation of the frequency of sister chromatid exchange (SCE) is accepted as a reliable cytogenetic method to assess the genotoxic effects of environmental factors.Materials and MethodsIn this study, the genotoxic effects of various NSAIDs were assessed in 30 patients to who they were administered following encluosed third molar surgery using SCE analysis before and after the operation. The frequency of SCE was evaluated before the operation and after 3 days of etodolac, nimesulid and naproxen use.ResultsThere was no statistically significant difference in the frequency of SCE between the preoperative and postoperative states in patients given etodolac, nimesulid or naproxen sodium.ConclusionShort term use of selective and non-selective NSAIDs was not associated with a significant genotoxic effect that could be detected using the SCE method in peripheric lymphocytes.

Chemoprevention of spontaneous development of hepatocellular carcinomas in fatty liver Shionogi mice by a cyclooxygenase‐2 inhibitor

Cyclooxygenase 2 (COX-2) and retinoid X receptor alpha (RXRalpha) are suggested to have roles in carcinogenesis. COX-2 inhibitors have been reported to suppress growth of hepatocellular carcinoma (HCC) cell lines in vitro. However, little is known about the preventive effect of these drugs on spontaneous hepatocarcinogenesis in vivo. Etodolac exists in a racemic mixture containing S- and R-etodolac. S-etodolac is responsible for COX-2 inhibitory activity and R-etodolac is related to the downregulation of RXRalpha. Here, the effect of etodolac on spontaneous development of HCC in fatty liver Shionogi mice is evaluated. Etodolac was administered at a low (2 mg/kg) or high (10 mg/kg) dose three times a week for 16 months starting at the age of 3 months. The development of HCC was suppressed slightly in the high-dose group, and suppressed markedly in the low-dose group, although the development of fatty liver was not inhibited in either group. Plasma prostaglandin E2 levels were also decreased significantly in the low-dose group, consistent with the suppression of HCC. The expression of RXRalpha and proliferating cell nuclear antigen in non-tumorous liver tissues was decreased significantly in both the low-dose and high-dose groups. These findings show that etodolac treatment at an optimum dose suppresses hepatocarcinogenesis in vivo, and may be useful for preventing the development of HCC in humans.

Inhibitory effects of etodolac, a selective COX-2 inhibitor, on the occurrence of tumors in colitis-induced tumorigenesis model in rats

Ulcerative colitis (UC)-associated neoplasia is one of the complications seen in patients with long-standing UC. Based on many epidemiological studies, colitis is assumed to promote colon tumorigenesis. Tumorigenesis is known to be suppressed in rodents and humans by selective cyclooxygenase-2 inhibitors. However, whether these drugs would serve as protective agents against UC-associated neoplasia remains unclear. Therefore, using a colitis-induced tumorigenesis rat model, we investigated the effects of etodolac, a selective cyclooxygenase-2 inhibitor, on tumorigenesis. The following 4 groups were examined: group A, administered trinitrobenzene sulfonic acid and 1,2-dimethylhydrazine; group B, in addition to the treatment in group A, also received etodolac; group C, administered etodolac alone; and group D, did not receive any agent throughout the study and served as an untreated control. The rats were sacrificed 163 days after the start of experiment, and the number of aberrant crypt foci and tumors in the intestine were counted using a stereoscopic microscope following methylene blue staining. The mean number of aberrant crypt foci was 52.4 in group A, 18.9 in group B, 0 in group C and 0.5 in group D. A total of 9 tumors were observed in group A alone, with none in the remaining groups. The numbers of aberrant crypt foci and tumors in group B were significantly lower than in group A. Etodolac, a selective cyclooxygenase-2 inhibitor, suppresses the occurrence of aberrant crypt foci and tumors in colitis-induced tumorigenesis in rats.

Effect of etodolac, a COX-2 inhibitor, on neuropathic pain in a rat model

Etodolac, a cyclooxygenase-2 inhibitor, may alleviate nociceptive pain and inhibit the activation of osteoclasts. The aim of the present study was to determine whether etodolac can alleviate heat-evoked hyperalgesia and investigate its possible protective effects on osteoporosis induced by chronic constriction injury (CCI) in rats. A CCI to the sciatic nerve was performed, after which the rats received etodolac orally in a volume of 2 ml at 0, 1, and 10 mg/kg/day for 1 to 5 weeks following surgery (experiment 1); at 0 and 10 mg/kg/day for 1 day to 5 weeks following surgery (experiment 2); and at 0 mg/kg/day for 1 to 5 weeks, 10 mg/kg/day for 1 to 2 weeks after surgery, or 10 mg/kg/day for 1 to 3 weeks after surgery (experiment 3). Paw withdrawal latency after exposure to heat, bone mineral content (BMC) and bone mineral density (BMD) in the whole tibial bone, and the number of tartrate resistant acid phosphate (TRAP)-positive multinucleated osteoclasts were measured. Etodolac alleviated heat-evoked hyperalgesia in the CCI rats and the increase in number of TRAP-positive multinucleated osteoclasts on the CCI-side was abrogated, however, it did not inhibit the decrease of BMC and BMD on the CCI-side. Our results suggest that etodolac is useful for treatment of neuropathic pain.

Combined treatment with selective cyclooxygenase-2 inhibitor and fluorinated pyrimidines for liver metastasis of colon cancer

Liver metastasis is a major contributor to mortality in patients with colorectal cancer. Hence, it is essential to establish preventive therapy to control liver metastasis. Recently, it has become widely accepted that cyclooxygenase (COX)-2 inhibitors possess anti-cancer activity for various types of tumor, especially colorectal. The clinical application of COX-2 inhibitors may therefore be beneficial. In this study, we have developed a combined treatment with a selective COX-2 inhibitor and fluorinated pyrimidines for liver metastasis of colorectal cancer, and examined the effect of these agents on proliferation and invasion of a highly metastatic human colon cancer cell line, LM-H3. The COX-2 inhibitor etodolac was found to inhibit cell invasion of LM-H3. 5-Fluorouracil (5-FU) inhibited proliferation of this line in vitro. Etodolac did not increase the inhibitory effect of 5-FU on cell proliferation. We also examined the inhibitory effect of etodolac and UFT, belonging to the fluorinated pyrimidines, on liver metastasis by using a liver metastatic model in the nude mouse. Combined treatment with etodolac and UFT markedly reduced liver metastasis. Serious side effects were not observed. In conclusion, combined treatment with etodolac and UFT might be a promising preventive therapy for liver metastasis of colon cancer.

Effects of etodolac, a selective cyclooxygenase-2 inhibitor, on the expression of E-cadherin-catenin complexes in gastrointestinal cell lines.

Recent studies have shown that cyclooxygenase-2 (COX-2) inhibitors may participate in the proliferation of cancer cells. Because the cadherin-catenin complex is not only a key component of the adherens junction but also has been suggested to regulate cell proliferation, modulation of these molecules may be a mechanism by which COX-2 activity affects cell proliferation. In this study, we evaluated the effect of a COX-2 inhibitor on the proliferation and expression of E-cadherin-complexes in gastrointestinal cancer cell lines. The gastrointestinal cancer cell lines Caco2, HT29, and MKN45 were grown for 24 h in the presence and absence of a selective COX-2 inhibitor, etodolac (10(-5), 10(-4), and 10(-3) M). Cell proliferation was assessed by (3)H-thymidine incorporation, and the expression of E-cadherin and catenins was assessed by Western blotting, Northern blotting, and immunofluorescence. Etodolac induced a significant reduction in cell proliferation in Caco2 and MKN45 cells. E-cadherin expression was upregulated after stimulation with etodolac in Caco2 cells, whereas the expression of alpha-, beta-, gamma- and p120-catenins was not modified. The expression of E-cadherin mRNA was also upregulated in Caco2 cells, and was upregulated also in MKN45 cells, which did not express normal E-cadherin protein by the use of a mouse monoclonal antibody against human E-cadherin, HECD-1 antibody. Immunofluorescence revealed that the increased E-cadherin was localized at the cytoplasmic membrane. The inhibition of cell growth by etodolac in Caco-2 cells was associated with a dose-dependent upregulation and intense cytoplasmic localization of E-cadherin. No quantitative change in catenin expression was found in this phenomenon. These findings suggest that the COX-2 inhibitor affects the transcription of E-cadherin, or that there may be some homeostatic link between the cell cycle and E-cadherin transcription.

The effect of etodolac on bile salt and histamine-mediated gastric mucosal injury in the rat

The effect of the selective cyclo-oxygenase-type-2 (COX-2) inhibitor etodolac on gastric mucosal integrity and gastric acid secretion was investigated in the rat. Etodolac was given in doses comparable with those being used in man for therapy of rheumatic conditions. The effect of etodolac was studied in the presence of a mild barrier breaker and in the presence of increased rates of endogenous acid secretion. In conscious pylorus-ligated rats, etodolac given intragastrically in 16 or 32 mg /kg for 3 h did not by itself give rise to visible gastric mucosal injury. Etodolac, however, exacerbated gastric mucosal injury evoked by intragastric application of acidified sodium taurocholate (5 mM in 150 mM HCl) in a dose-dependent manner. This effect of edotolac was independent of changes in gastric acid secretory responses. In rats whose gastric acid secretion was stimulated by intraperitoneal histamine (5 mg/kg), and etodolac (given i.g. in doses of 16 or 32 mg/kg) also increased gastric mucosal injury caused by histamine dose-dependently in the 3-h pylorus-ligated rats. Etodolac decreased gastric mucus in the saline- and in the sodium taurocholate-treated rats. In urethane-anaesthetized acute gastric fistula rats, intragastric etodolac (32 mg/kg) did not modify basal gastric acid secretion. Our data suggest that etodolac, a selective COX-2 inhibitor, impairs gastric mucosal resistance and can exacerbate gastric mucosal injury caused by other mucosal barrier breaking agents. Cyclooxygenase type-2 thus contributes to the gastric mucosal defences.

Effect of etodolac, a selective cyclooxygenase-2 inhibitor on the expression of the E-cadherin-catenin complexes in gastrointestinal cell lines

Effect of etodolac, a selective cyclooxygenase-2 inhibitor on the expression of the E-cadherin-catenin complexes in gastrointestinal cell lines

Clinical effects of etodolac and tiaprofenic acid in impacted third molar surgery

Clinical effects of etodolac and tiaprofenic acid in impacted third molar surgery