title: Effect of N-acetylcysteine on the murine model of colitis induced by dextran sodium sulfate through up-regulating PON1 activity.
abstract: Reactive oxygen species (ROS) are increased in inflammatory bowel disease (IBD) and have been implicated as mediators of intestinal inflammation. We investigated the hypothesis that N-acetylcysteine (NAC) as a glutathione (GSH) precursor attenuates disease progression in a murine dextran sodium sulfate (DSS)-induced colitis model. A colitis model was induced by adding 5% DSS into the drinking water for 7 days. BALB/c mice were injiciatur enema with saline, 5-ASA, N-acetylcysteine, respectively, and free drinking water as control group. DSS-treated mice developed severe colitis as shown by bloody diarrhea, weight loss, and pathologic involvement. Colon lengths were significantly decreased in DSS-treated mice with decreased GSH activity too (P < 0.01). ROS in the colon, the level of interleukin 1 beta (IL-1 beta) in colonic mucosa, serum tumor necrosis factor a (TNF-alpha), MPO, and MDA were significantly increased in DSS-treated animals (P < 0.01), with decreased PON1 activity (P < 0.01). However, NAC significantly decreased colonic MPO activity, ROS, TNF-alpha and IL-1 beta levels and increased PON1 activity and GSH concentration. Moreover, NAC attenuated the macroscopic colonic damage and the histopathologic changes-induced by DSS while similar to 5-ASA group. These results suggest that NAC may be effective in the treatment of colitis through its up-regulating PON1 and scavenging oxygen-derived free radicals.
authors.affiliation: The Digestive Department, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: You
authors.forename: Jian-Jiang
authors.initials: JJ
authors.lastname: Fu
authors.forename: Jun
authors.initials: J
authors.lastname: Meng
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Huang
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Liu
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D043303:Aryldialkylphosphatase / Q000378:metabolism*; D003092:Colitis / Q000139:chemically induced* / Q000378:metabolism* / Q000517:prevention & control; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate / Q000009:adverse effects*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D053583:Interleukin-1beta; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D016264:Dextran Sulfate; D009195:Peroxidase; D043303:Aryldialkylphosphatase; D005978:Glutathione; D000111:Acetylcysteine