title: Protective effects of N-acetylcysteine on acetic acid-induced colitis in a porcine model.
abstract: BACKGROUND
  Ulcerative colitis is a chronic inflammatory disease and involves multiple etiological factors. Acetic acid (AA)-induced colitis is a reproducible and simple model, sharing many characteristics with human colitis. N-acetylcysteine (NAC) has been widely used as an antioxidant in vivo and in vitro. NAC can affect several signaling pathways involving in apoptosis, angiogenesis, cell growth and arrest, redox-regulated gene expression, and inflammatory response. Therefore, NAC may not only protect against the direct injurious effects of oxidants, but also beneficially alter inflammatory events in colitis. This study was conducted to investigate whether NAC could alleviate the AA-induced colitis in a porcine model.
  
  
  METHODS
  Weaned piglets were used to investigate the effects of NAC on AA-induced colitis. Severity of colitis was evaluated by colon histomorphology measurements, histopathology scores, tissue myeloperoxidase activity, as well as concentrations of malondialdehyde and pro-inflammatory mediators in the plasma and colon. The protective role of NAC was assessed by measurements of antioxidant status, growth modulator, cell apoptosis, and tight junction proteins. Abundances of caspase-3 and claudin-1 proteins in colonic mucosae were determined by the Western blot method. Epidermal growth factor receptor, amphiregulin, tumor necrosis factor-alpha (TNF-α), and toll-like receptor 4 (TLR4) mRNA levels in colonic mucosae were quantified using the real-time fluorescent quantitative PCR.
  
  
  RESULTS
  Compared with the control group, AA treatment increased (P < 0.05) the histopathology scores, intraepithelial lymphocyte (IEL) numbers and density in the colon, myeloperoxidase activity, the concentrations of malondialdehyde and pro-inflammatory mediators in the plasma and colon, while reducing (P < 0.05) goblet cell numbers and the protein/DNA ratio in the colonic mucosa. These adverse effects of AA were partially ameliorated (P < 0.05) by dietary supplementation with NAC. In addition, NAC prevented the AA-induced increase in caspase-3 protein, while stimulating claudin-1 protein expression in the colonic mucosa. Moreover, NAC enhanced mRNA levels for epidermal growth factor and amphiregulin in the colonic mucosa.
  
  
  CONCLUSIONS
  Dietary supplementation with NAC can alleviate AA-induced colitis in a porcine model through regulating anti-oxidative responses, cell apoptosis, and EGF gene expression.
authors.affiliation: Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China. houyq@aliyun.com.
authors.forename: Qingjing
authors.initials: Q
authors.lastname: Wang
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Hou
authors.forename: Dan
authors.initials: D
authors.lastname: Yi
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Binying
authors.initials: B
authors.lastname: Ding
authors.forename: Xing
authors.initials: X
authors.lastname: Chen
authors.forename: Minhui
authors.initials: M
authors.lastname: Long
authors.forename: Yulan
authors.initials: Y
authors.lastname: Liu
authors.forename: Guoyao
authors.initials: G
authors.lastname: Wu
mesh_terms: D019342:Acetic Acid; D000111:Acetylcysteine / Q000494:pharmacology* / Q000627:therapeutic use; D066258:Amphiregulin; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D062445:Claudin-1 / Q000187:drug effects / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D003093:Colitis, Ulcerative; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019587:Dietary Supplements; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D066255:EGF Family of Proteins; D004815:Epidermal Growth Factor / Q000097:blood / Q000187:drug effects; D066246:ErbB Receptors / Q000187:drug effects / Q000235:genetics; D016166:Free Radical Scavengers / Q000494:pharmacology* / Q000627:therapeutic use; D006023:Glycoproteins / Q000187:drug effects / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D015850:Interleukin-6 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013552:Swine; D051197:Toll-Like Receptor 4 / Q000187:drug effects / Q000235:genetics; D016211:Transforming Growth Factor alpha / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
chemical_list: C587848:AREG protein, human; D066258:Amphiregulin; D062445:Claudin-1; D066255:EGF Family of Proteins; D016166:Free Radical Scavengers; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D051197:Toll-Like Receptor 4; D016211:Transforming Growth Factor alpha; D014409:Tumor Necrosis Factor-alpha; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D053148:Caspase 3; D015232:Dinoprostone; D019342:Acetic Acid; D000111:Acetylcysteine