Abstract
BackgroundUlcerative 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.MethodsWeaned 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.ResultsCompared 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.ConclusionDietary supplementation with NAC can alleviate AA-induced colitis in a porcine model through regulating anti-oxidative responses, cell apoptosis, and EGF gene expression.
Highlights
Ulcerative colitis is a chronic inflammatory disease and involves multiple etiological factors
Concentrations of DNA, RNA and protein in the colonic mucosa Compared with the control group, Acetic acid (AA) treatment reduced protein/DNA ratio (P < 0.05) in the colonic mucosa (Table 4)
A piglet model of ulcerative colitis was successfully developed by intrarectal administration of 10 mL of 10% AA
Summary
Ulcerative colitis is a chronic inflammatory disease and involves multiple etiological factors. NAC may protect against the direct injurious effects of oxidants, and beneficially alter inflammatory events in colitis. N-acetylcysteine (NAC), the precursor of L-cysteine and reduced glutathione, has been widely used as an antioxidant in vivo and in vitro [1]. Oxidative stress have an important bearing on inflammation via the activation of redoxsensitive transcriptional factors such as nuclear factor kB (NF-kB) and activator protein 1, which regulate expression of key genes encoding pro-inflammatory mediators and protective antioxidant proteins. In support of this view, pharmacological agents that lower the amounts of reactive oxygen metabolites may reduce inflammation [13]. Acetic acid (AA)-induced colitis is a reproducible and simple model, sharing many characteristics with human colitis [11,16]
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