Cyclooxygenase-2 (Cox-2) is over-expressed in prostate cancer (PCa) and involved in its development and progression by facilitating inflammatory response, reducing cell apoptosis, increasing angiogenesis and damaging DNA oxidation. Selective Cox-2 inhibitors suppress PCa growth through various channels and therefore have a promising application value in the management of prostate cancer.
Apoptosis ; Cyclooxygenase 2 ; metabolism ; Cyclooxygenase 2 Inhibitors ; therapeutic use ; Humans ; Male ; Prostatic Neoplasms ; drug therapy ; metabolism

OBJECTIVETo examine the chemopreventive effect of selective cyclooxygenase-2 (COX-2) inhibitor celecoxib for Barrett's esophagus in rats.

METHODSFifty 8-week-old male Sprague Dawley rats underwent esophagojejunostomy to induce Barrett's esophagus model. Four weeks after operation the animals were given celecoxib 10 mg/(kg*d(-1))(celecoxib group), or saline 1 ml (control group). Another 10 rats were sham operation group. All animals were sacrificed at 20 week after surgery. The degree of inflammation, Barrett's esophagus, adenocarcinoma, COX-2 expression and PGE(2) of animals were assessed.

RESULTAmong 60 rats, 6 rats died in celecoxib group, 8 rats died in control group, 1 rat died in sham operation group, and 45 (75%) rats completed the study. The incidence of mild, moderate and severe degree esophageal inflammation in celecoxib group and control group was 14/19(73.68%), 4/19(21.05%), 1/19(5.26%); 4/17(23.53%), 5/17(29.41%), 8/17(47.06%)(P<0.05), respectively. The incidence of Barrett's esophagus was 7/19(36.84%), 13/17(76.47%) in two group respectively(P<0.05); The incidence of Barrett's esophagus with dysplasia was 2/19(10.53%), 8/17(47.06%)(P<0.05), respectively. The expression of COX-2 was 1/7(14.29%), 10/13(76.92%)(P<0.05) in two groups. PGE2 content was significantly lower in the celecoxib group than that in control group(P<0.001). No esophageal pathological changes were found in sham operation group.

CONCLUSIONSelective COX-2 inhibitors celecoxib can inhibit inflammations, development of Barrett's esophagus and esophagus adenocarcinoma.

Animals ; Barrett Esophagus ; metabolism ; prevention & control ; Celecoxib ; Cyclooxygenase 2 ; metabolism ; Cyclooxygenase 2 Inhibitors ; therapeutic use ; Dinoprostone ; metabolism ; Male ; Pyrazoles ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Sulfonamides ; therapeutic use

The cyclooxygenase (COX) is a key enzyme in the coversion of arachidonic acid to prostaglandins. COX-1 is constitutively expressed and is a critical housekeeping gene, whereas COX-2 is rapidly upregulated by growth factors and cytokines and thus responsible for inflammation. COX-2 is frequently overexpressed in colonic adenoma and carcinoma. Specific inhibitors of COX-2 have been shown to induce apoptosis in tumor cells and to inhibit tumor growth in animal models and in humans. Long-standing IBD patients have increased risk of developing colorectal cancer compared to general population. IBD-associated colorectal carcinogenesis is probably promoted by chronic inflammation and closely related to COX-2. In a recent study, powerful chemopreventive ability of selective COX-2 inhibitor was observed in colitis-related colon carcinogenesis in mouse model. But it was reported that even selective COX inhibitors aggravated the DSS-induced colonic inflammation. It is assumed that endogenous PGs are involved in the mucosal defense against DSS-induced colonic ulcerations which are produced by COX-1 at early phase and by COX-2 at late phase. Long-term use of COX-2 inhibitors for the chemoprevention of colitic cancer is needed to define their mechanism of action, that reduce side effects and have specific tumor target.
Animals ; Colitis, Ulcerative/*drug therapy ; Colonic Neoplasms/diagnosis ; Cyclooxygenase 1/metabolism ; Cyclooxygenase 2/metabolism ; Cyclooxygenase 2 Inhibitors/pharmacology/*therapeutic use ; Humans ; Mice ; Models, Animal

OBJECTIVESTo investigate the effect of selective cyclooxygenase-2 (COX-2) inhibitor on alcohol-induced liver injury in rats.

METHODS58 male Wistar rats were randomly divided into three groups: control group treated with dextrose and corn oil, model group with ethanol and corn oil, treatment group with corn oil and ethanol plus a selective COX-2 inhibitor celecoxib. All treatments were injected into stomach through intragastric tubes. Liver samples were analyzed for histopathology with light microscope (LM) and transmission electron microscope (TEM), and the expression of COX-2 with western blotting. Levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum, levels of 6-Keto-prostaglandin F1 alpha (6-k-PGF1a) and thromboxane B2 (TXB2) in liver, and activity of glutathione s-transferase (GST) both in liver tissue and in plasma were measured.

RESULTSLM and TEM indicated hepatocytes were injured obviously in the model group and slightly in the treatment group. The levels of AST and ALT in serum, TXB2 in liver and the activity of GST in plasma increased significantly in the model group (t> or =2.294, P<0.05), but the activity of GST in liver decreased significantly (t=8.856, P<0.01) compared with those in the control group. To compare with the model group, the levels of AST and TXB2 decreased significantly (t=4.305, P<0.01; t=2.799, P<0.01), meanwhile the activity of GST increased significantly (t=10.134, P<0.01) in the treatment group. COX-2 expression in liver by western blotting increased significantly in the model group, compared with the control group (t=4.067, P<0.01) and the treatment group (t=2.251, P<0.05). Exceptionally, the level of 6-k-PGF1a decreased significantly (t=2.284, P<0.05) in the model group.

CONCLUSIONCOX-2 has involved in the alcohol-induced liver injury, and its inhibitor can diminish alcohol-induced liver injury in rats through decreasing TXB2 level

Animals ; Cyclooxygenase 2 ; Cyclooxygenase 2 Inhibitors ; Cyclooxygenase Inhibitors ; therapeutic use ; Disease Models, Animal ; Ethanol ; Isoenzymes ; antagonists & inhibitors ; Liver Diseases, Alcoholic ; prevention & control ; Male ; Prostaglandin-Endoperoxide Synthases ; Protective Agents ; therapeutic use ; Rats ; Rats, Wistar ; Thromboxane B2 ; metabolism

Cyclooxygenase (COX) is the obligate, rate-limiting enzyme for the conversion of arachidonic acid into prostaglandins, which mediate mitogenesis, apoptosis, angiogenesis, blood flow, secondary injury, and inflammation. COX is consist of 2 subtypes: COX-1 and COX-2. In recent years, there are a number of lines of evidence that COX-1 and COX-2 play a important in role brain injuries.
Animals ; Apoptosis/drug effects* ; Brain Injuries/pathology* ; Cyclooxygenase 1/metabolism* ; Cyclooxygenase 2/metabolism* ; Cyclooxygenase Inhibitors/therapeutic use* ; Humans ; Immunohistochemistry ; Neurons/drug effects* ; Rats ; Time Factors

BACKGROUND/AIMS: To investigate the degree of cyclooxygenase-2 (COX-2) protein expression in chronic hepatitis and cirrhosis. METHODS: COX-2 protein expression was evaluated in 43 cases of chronic hepatitis and 24 cases of cirrhosis using immunohistochemical techniques. The COX-2 immunohistochemical staining score was assessed using the scoring systems of Pazirandeh et al and Qiu et al. and each scoring system was based on a sum of the parameters of staining intensity and distribution. RESULTS: The mean COX-2 expression scores in chronic hepatitis and cirrhosis were 2.5 +/- 1.3 vs. 3.3 +/- 1.1 (p = 0.008), and 3.2 +/- 2.0 vs. 4.5 +/- 1.7 (p = 0.006), respectively, based on the Pazirandeh et al. and Qiu et al. scoring systems. The percentage samples of high COX-2 expression score (4 to 5) in chronic hepatitis and cirrhosis were 16.3% vs. 45.8% (p = 0.022), and 23.3% vs. 50% (p = 0.021), respectively, based on the two scoring systems. The mean COX-2 expression scores based on the severity of hepatic fibrosis scored using Ishak's modified staging system (fibrosis score 0 to 3 vs. 4 to 6) were 2.4 +/- 1.3 vs. 3.2 +/- 1.1 (p = 0.009), and 3.1 +/- 2.0 vs. 4.3 +/- 1.8 (p = 0.009), respectively, based on the two scoring systems. CONCLUSIONS: COX-2 expression was significantly higher in liver cirrhosis group than in chronic hepatitis. COX-2 expression scores according to Ishak's staging was significantly higher in the advanced fibrosis group. COX-2 may play a role in the progression of hepatic fibrosis.
Adult ; Aged ; Cyclooxygenase 2/analysis/*physiology ; Cyclooxygenase 2 Inhibitors/therapeutic use ; Disease Progression ; Female ; Hepatitis, Chronic/enzymology ; Humans ; Immunohistochemistry ; Liver Cirrhosis/drug therapy/*enzymology ; Male ; Middle Aged

OBJECTIVETo evaluate the clinical efficiency of selective cyclo-oxygenase-2 (COX-2) inhibitor compared to traditional nonselective NSAIDs for the prevention of heterotopic ossification (HO) after total hip arthroplasty (THA).

METHODSBy searching Medline, Embase, CENTRAL (Cochrane Central Register of Controlled Trials) and Science Citation Index et al, only randomised controlled studies of selective COX-2 inhibitors VS nonselective COX-1 and COX-2 inhibitors for the prevention of HO after THA were included. The quality assessment of included studies was evaluated according to the standard of the Cochrane Collaboration, and the data were analysised by statistic software Stata 10.0. The HO incidence of both groups in different degrees was compared.

RESULTSFour eligible randomised controlled trials of totally 808 patients were included. Meta-analysis results showed that no statistically significant difference was found in overall incidence of HO (RR = 1.08, 95% CI: 0.71-1.64,P = 0.73), incidence of moderate severe HO (Brooker II and III) (RR = 0.83, 95% CI: 0.48-1.42, P = 0.49) and any grade of Brooker classification between two groups. In all included studies, 16 patients receiving nonselective COX inhibitor (4.4%) discontinued treatment because of gastrointestinal toxicity,whereas 10 patients in the selective COX-2 inhibitor group (2.7%) discontinued for gastrointestinal side effects.

CONCLUSIONThe selective COX-2 inhibitors are as equally effective as nonselective NSAIDs for the prevention of HO after THA. Considering the side effects of nonselective NSAIDs, selective COX-2 inhibitors were recommend for the prevention of HO after THA.

Anti-Inflammatory Agents, Non-Steroidal ; adverse effects ; therapeutic use ; Arthroplasty, Replacement, Hip ; adverse effects ; Cyclooxygenase 2 Inhibitors ; adverse effects ; therapeutic use ; Cyclooxygenase Inhibitors ; adverse effects ; therapeutic use ; Humans ; Ossification, Heterotopic ; prevention & control ; Randomized Controlled Trials as Topic

OBJECTIVETo systematically evaluate the efficacy and safety of preoperative administration of cyclooxygenase-2 (COX-2) inhibitor on pain occurring with total knee arthroplasty (TKA).

METHODSWe electronically searched PubMed, Cochrane Library, EMBASE, CNKI, CBM, Wanfang data from inception to March 15, 2014 and manual searched journal of library collection to identify randomized controlled trials (RCTs) about preoperative administration of COX-2 inhibitor on pain occurring with TKA. The methodological quality of the included RCTs was assessed and the data were extracted according to the Cochrane Handbook 5.1.0. Meta-analysis was performed by using RevMan 5.2 software.

RESULTSA total of 6 RCTs involving 228 patients were included. The results of meta-analyses showed that: (1) Efficacy: The visual analog scale (VAS) of post-operation at 12-hour (WMD = -0.60, 95% CI -0.83 to -0.37, P < 0.000 01) and 24-hour (WMD = -0.74, 95% CI -1.29 to - 0.19, P = 0.008) was decreased when COX-2 inhibitor was used before operation. And compared with control group, experimental group decreased the modified numerical pain rating scale (MNPRS) at 24-hour (WMD = -0.50, 95% CI -0.70 to -0.30, P < 0.000 01), 48-hour (WMD = -0.55,95% CI -0.65 to -0.45,P < 0.000 01) under quiescent conditions, and the same result at 24-hour (WMD = -0.82, 95% CI -1.26 to -0.38, P <0.000 01), 48-hour (WMD = -0.71, 95% CI -0.82 to -0.60, P < 0.000 01) under active conditions. The morphine consumption postoperatively were fewer in experimental group at the first day (WMD = - 1.35, 95% CI -1.92 to -0.79, P < 0.000 01) and the second day (WMD = -1.60, 95% CI -2.68 to -0.52, P = 0.004). (2) Safety: COX-2 inhibitor could lessen the incidence of postoperative pruritus (RR = 0.35, 95% CI 0.15 to 0.84, P = 0.02), but not statistically decrease of nausea and vomiting (RR = 0.83, 95% CI 0.54 to 1.28, P = 0.40) and exhaustion (RR = 0.63, 95% CI 0.05 to 7.67, P = 0.72).

CONCLUSIONThe current evidence indicated that preoperative administration of COX-2inhibitor can effectively improve the effect of postoperative analgesia, reduce the consumption of morphine and lessen the incidence of pruritus. Due to the limited quantity of the included studies and the evidence with limited strength,further high-quality RCTs are needed to verify the aforementioned conclusion.

Arthroplasty, Replacement, Knee ; Cyclooxygenase 2 Inhibitors ; therapeutic use ; Humans ; Pain, Postoperative ; drug therapy ; Postoperative Complications ; prevention & control ; Pruritus ; prevention & control

Objective: To investigate whether the selective cyclooxygenase-2 enzyme inhibitors celecoxib has protective effect on the liver of rats with type 2 diabetes mellitus (T2DM) combined with nonalcoholic steatohepatitis (NASH) via inhibiting the expression of Rho/ROCK pathway. Methods: Forty male SD rats were randomly divided into four groups: type 2 diabetes mellitus combined with nonalcoholic steatohepatitis (T2DM-NASH) group, T2DM-NASH + celecoxib group, control group, and control+celecoxib group. The T2DM-NASH and T2DM-NASH + celecoxib groups were fed with high-sugar and fat diet, and the control group and control + celecoxib group were fed with basal diet (25 kJ/kg). Four weeks later, streptozotocin (STZ, 30 mg/kg) was intraperitoneally injected into the NASH group and T2DM-NASH + celecoxib group to induce T2DM model, and the control group and control + celecoxib group were intraperitoneally injected with isovolumic citric acid-sodium citrate buffer. Four weeks after STZ injection, the T2DM-NASH + celecoxib group and the control + celecoxib group were gavaged with celecoxib (10 mg·kg·d) dissolved in normal saline for 4 weeks, and the remaining two groups of rats were gavaged with isovolumic normal saline for 4 weeks. Animals were sacrificed at the end of the 12- weeks, and the liver tissue was collected. Liver pathological changes were observed by HE staining. The expressions of RhoA, RhoA, ROCK1 and ROCK2 proteins in liver were detected by immunohistochemistry and western blot. The expressional condition of RhoA, ROCK1 and ROCK2 mRNA in liver were detected by real-time quantitative PCR. The differences were compared between protein and mRNA expression among the groups by analysis of variance and t-test. Results: Compared with the control group and the control + celecoxib group, the liver tissue of the T2DM-NASH group and the T2DM-NASH + celecoxib group had severe steatosis, and there was partial inflammatory cell infiltration under the light microscope. The expression levels of RhoA, ROCK1 and ROCK2 protein and mRNA were significantly increased (P < 0.05) in each liver tissue, while liver steatosis was reduced to certain extent in T2DM-NASH + celecoxib group than T2DM-NASH group, and the expression levels of RhoA, ROCK1 and ROCK2 protein and mRNA were decreased in each liver tissue of T2DM-NASH group (P < 0.05). Conclusion: The selective cyclooxygenase-2 enzyme inhibitors celecoxib has a protective effect on the liver of rats with T2DM-NASH, and its effect may be achieved by inhibiting the expression of Rho/ROCK pathway.
Animals ; Cyclooxygenase 2/therapeutic use* ; Cyclooxygenase 2 Inhibitors/therapeutic use* ; Diabetes Mellitus, Type 2/drug therapy* ; Liver ; Male ; Non-alcoholic Fatty Liver Disease/drug therapy* ; Rats ; Rats, Sprague-Dawley

AIM: In the present study, the anti-inflammatory and antioxidant activities of the methanol extract of Ruta graveolens leaves (RG-M) were evaluated using various in vivo and in vitro models. METHOD: For anti-inflammatory activity, RG-M was administered by the oral route (p.o.) in a carrageenan-induced paw edema model, and by the intraperitoneal route (i.p.) in an exudative inflammation model. In vitro inhibition of cyclooxygenase and lipoxygenase enzymes was evaluated. In vitro antioxidant activity was also examined. Endogenous antioxidant status was further evaluated by ferric reducing ability of plasma model. RESULTS: RG-M showed maximum inhibition of carrageenan-induced edema (100 mg·kg⁻¹ - 33.36%; 200 mg·kg⁻¹ - 45.32% and 400 mg·kg⁻¹ - 56.28%). In the exudative inflammation model, a significant reduction in leukocyte migration (200 mg·kg⁻¹ - 54.75% and 400 mg·kg⁻¹ - 77.97%) and protein exudation (200 mg·kg⁻¹ - 31.14% and 400 mg·kg⁻¹ - 49.91%) were observed. RG-M also exhibited inhibition of COX-1 (IC50 182.27 μg·mL⁻¹) and COX-2 (IC50 190.16 μg·mL⁻¹) as well as 5-LOX (IC50 215.71 μg·mL⁻¹). Antioxidant activity was significant with improved endogenous antioxidant status. CONCLUSION The results demonstrated the anti-inflammatory and antioxidant activity of RG-M with potent inhibitory effects on the arachidonic acid pathways.
Animals ; Anti-Inflammatory Agents ; pharmacology ; therapeutic use ; Antioxidants ; pharmacology ; therapeutic use ; Arachidonic Acid ; metabolism ; Carrageenan ; Cyclooxygenase 1 ; metabolism ; Cyclooxygenase 2 ; metabolism ; Cyclooxygenase Inhibitors ; pharmacology ; therapeutic use ; Disease Models, Animal ; Edema ; drug therapy ; Exudates and Transudates ; Ferric Compounds ; metabolism ; Inflammation ; drug therapy ; metabolism ; Leukocytes ; metabolism ; Lipoxygenase Inhibitors ; pharmacology ; therapeutic use ; Lipoxygenases ; metabolism ; Male ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Plant Leaves ; Rats, Wistar ; Ruta