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Effect of N-acetylcysteine on the Murine Model of Colitis Induced by Dextran Sodium Sulfate Through Up-Regulating PON1 Activity

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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 1β (IL-1β) in colonic mucosa, serum tumor necrosis factor a (TNF-α), 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-α and IL-1β 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.

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Authors and Affiliations

  1. The Digestive Department of First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China

    Yu You & Guo-Dong Huang

  2. Department of Pharmacology, College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, 330004, China

    Jian-Jiang Fu & Yu-Hui Liu

  3. The JiangXi Provincial People’s Hospital, Nanchang, Jiangxi, 330006, China

    Jun Meng

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Correspondence to Yu-Hui Liu.

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You, Y., Fu, JJ., Meng, J. et al. Effect of N-acetylcysteine on the Murine Model of Colitis Induced by Dextran Sodium Sulfate Through Up-Regulating PON1 Activity. Dig Dis Sci 54, 1643–1650 (2009). https://doi.org/10.1007/s10620-008-0563-9

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