title: Ameliorative effects of sodium ferulate on experimental colitis and their mechanisms in rats.
abstract: OBJECTIVE
  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% (V/V) 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 with normal saline, 5-aminosalicylic acid (100 mg x kg(-1)), and SF at the doses of 200, 400 and 800 mg x kg(-1) respectively 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-kappaB) 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-kappaB p65 proteins in the colonic mucosa, although the colonic SOD activity was significantly decreased compared with the normal control (CMDI: 2.9+/-0.6 vs 0.0+/-0.0; HS: 4.3+/-0.9 vs 0.7+/-1.1; MPO: 98.1+/-26.9 vs 24.8+/-11.5; MDA: 57.53+/-12.36 vs 9.21+/-3.85; NO: 0.331+/-0.092 vs 0.176+/-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 vs 0.053+/-0.015; COX-2: 0.296+/-0.028 vs 0.034+/-0.013; NF-kappaB p65: 0.314+/-0.026 vs 0.039+/-0.012; SOD: 28.33+/-1.17 vs 36.14+/-1.91; P<0.01). However, these parameters were found to be significantly ameliorated in rats treated locally with SF at the given dose protocols, especially at 400 mg x kg(-1) and 800 mg x kg(-1) doses (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-kappaBp65: 0.215+/-0.019,0.189+/-0.016; SOD: 32.15+/-4.26, 33.24+/-3.69; P<0.05-0.01). Moreover, a therapeutic dose protocol of 800 mg x kg(-1) SF was observed as effective as 100 mg x kg(-1) of 5-ASA in the amelioration of colonic mucosal injury as evaluated by CMDI and HS.
  
  
  CONCLUSIONS
  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-kappaB expression.
authors: Department of Gastroenterology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, Hubei Province, China. dongwg@public.wh.hb.cn
authors: Wei-Guo
authors: WG
authors: Dong
authors: Shao-Ping
authors: SP
authors: Liu
authors: Bao-Ping
authors: BP
authors: Yu
authors: Dong-Fang
authors: DF
authors: Wu
authors: He-Sheng
authors: HS
authors: Luo
authors: Jie-Ping
authors: JP
authors: Yu
mesh_terms: D019342:Acetic Acid; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D003373:Coumaric Acids / Q000494:pharmacology*; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013929:Thromboxane B2 / Q000378:metabolism; D051996:Transcription Factor RelA
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003373:Coumaric Acids; D007527:Isoenzymes; D016328:NF-kappa B; D051996:Transcription Factor RelA; D013929:Thromboxane B2; C004999:ferulic acid; D019001:Nitric Oxide Synthase; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D019342:Acetic Acid