Ameliorative effects of sodium ferulate on experimental colitis and their mechanisms in rats

AIM: To investigate the ameliorative effects of sodium ferulate (SF) on acetic acid-induced colitis and their mechanisms in rats.METHODS: The colitis model of Sprague-Dawley rats was induced by intracolon enema with 8 % (WV) of acetic acid.The experimental animals were randomly divided into model control, 5-aminosalicylic acid therapy group and three dose of SF therapy groups. The 5 groups were treated intracolonically and daily (8:00 am) for 7 days 24 h following the induction of colitis. A normal control group of rats clystered with normal saline instead of acetic acid was also included in the study.Pathological changes of the colonic mucosa were evaluated by the colon mucosa damage index (CMDI) and the histopathological score (HS). The insulted colonic mucosa was sampled for a variety of determinations at the end of experiment when the animals were sacrificed by decapitation.Colonic activities of myeloperoxidase (MPO) and superoxide dismutase (SOD), and levels of malondialdehyde (MDA)and nitric oxide (NO) were assayed with ultraviolet spectrophotometry. Colonic contents of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2)were determined by radioimmunoassay. The expressions of inducible nitric oxide synthase (iNOS), cyclo-oxygenase-2 (COX-2) and nuclear factor kappa B (NF-κB) p65 proteins in the colonic tissue were detected with immunohistochemistry.RESULTS: Enhanced colonic mucosal injury, inflammatory response and oxidative stress were observed in the animals clystered with acetic acid, which manifested as the significant increase of CMDI, HS, MPO activities, MDA and NO levels,PGE2 and TXB2 contents, as well as the expressions of iNOS,COX-2 and NF-κB p65 proteins in the colonic mucosa,although the colonic SOD activity was significantly decreased compared with the normal control (CMDI: 2.9±0.6 vs0.0±0.0;HS: 4.3±0.9 vs0.7±1.1; MPO: 98.1±26.9 vs24.8±11.5; MDA:57.53±12.36 vs9.21±3.85; NO: 0.331±0.092 vs0.176±0.045;PGE2: 186.2±96.2 vs 42.8±32.8; TXB2: 34.26±13.51 vs 8.83±3.75; iNOS: 0.365±0.026 vs0.053±0.015; COX-2:0.296±0.028 vs0.034±0.013; NF-κB p65:0.314±0.026 vs 0.039±0.012; SOD: 28.33±1.17 vs36.14±1.91; P<0.01).However, these parameters were found to be significantly ameliorated in rats treated locally with SF at the given dose (CMDI: 1.8±0.8, 1.6±0.9; HS: 3.3±0.9, 3.1±1.0; MPO:63.8±30.5, 36.2±14.2; MDA: 41.84±10.62, 37.34±8.58; NO:0.247±0.042; 0.216±0.033; PGE2: 77.2±26.9, 58.4±23.9;TXB2:18.07±14.83; 15.52±8.62; iNOS:0.175±0.018, 0.106±0.019;COX-2: 0.064±0.018, 0.056±0.014; NF-κBp65: 0.215±0.019,0.189±0.016; SOD: 32.15±4.26, 33.24±3.69; P<0.05-0.01).amelioration of colonic mucosal injury as evaluated by CMDI and HS.CONCLUSION: Administration of SF intracolonically may have significant therapeutic effects on the rat model of colitis induced by acetic acid enema, which was probably due to the mechanism of antioxidation, inhibition of arachidonic acid metabolism and NF-κB expression.

Antiproliferative effect of octreotide on gastric cancer cells mediated by inhibition of Akt/PKB and telomerase

AIM: To investigate the antiproliferative effect of octreotide,a long-acting analogue of somatostatin, on gastric cancer cell line SGC7901 and its possible molecular mechanisms.METHODS: Gastric cancer cell line SGC7901 employed in the study was treated with 0.008, 0.04, 0.2, 1, 5 and 25μg@ml-1 of octreotide respectively for 24 h to evaluate the antiproliferative effect of somatostatin analog on the tumor cells by MTT assay method. To elucidate the underlying mechanism, the cells were exposed to 1 μg@ml-1 of octreotide for 0, 12, 24 and 48 h, when their Akt/PKB and telomerase activities were respectively determined using PCR-ELSIA and nonradioactive protein kinase assay protocols. The same experimental procedures were also performed in the control cells that were treated with corresponding vehicles instead of somatostatin analog.RESULTS: After exposed to octreotide for 24 h at the concentrations of more than 1 μg@ml-1 SGC7901 cells exhibited a dose-dependent inhibition of growth with the inhibiting rate to be as high as 34.66 % when 25 μg@ml-1 of octreotide was applied. The Akt/PKB and telomerase activity of SGC7901 cells was significantly inhibited when the cells were exposed to 1 μg@ml-1 of octreotide for 12, 24 and 48 h compared with that of their control counterparts (P＜0.01),both of which exhibited in a time-dependent manner.CONCLUSION: The antiproliferative effect of octreotide on SGC7901 cells might be mediated by the inhibition of Akt/PKB and telomerase.