N-acetylcysteine improves redox status, mitochondrial dysfunction, mucin-depleted crypts and epithelial hyperplasia in dextran sulfate sodium-induced oxidative colitis in mice

• Published in: European journal of pharmacology Vol. 691; no. 1-3; pp. 209 - 217
• Main Authors: Amrouche-Mekkioui, Ilhem, Djerdjouri, Bahia
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.09.2012
• Subjects: abscess; Acetylcysteine - pharmacology; Acetylcysteine - therapeutic use; animal models; Animals; antioxidants; Antioxidants - pharmacology; Antioxidants - therapeutic use; apoptosis; Apoptosis - drug effects; Biomarkers - metabolism; catalase; colitis; Colitis - chemically induced; Colitis - drug therapy; Colitis - metabolism; Colitis - pathology; colon; Colon - drug effects; Colon - metabolism; Colon - pathology; colorectal neoplasms; dextran; Dextran sodium sulfate; Dextran Sulfate - pharmacology; diet; drinking water; epithelial cells; Epithelial Cells - drug effects; Epithelial Cells - pathology; glutathione; Hyperplasia; Hyperplasia - drug therapy; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; lipids; Male; malondialdehyde; Mice; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondria - pathology; Mucin-depleted crypt; mucins; Mucins - deficiency; myeloperoxidase; N-acetylcysteine; nitric oxide; oxidation; Oxidation-Reduction - drug effects; Oxidative colitis; Oxidative Stress - drug effects; pharmacology; reactive oxygen species; sodium sulfate; thiols; Mucin-depleted crypt; Dextran sodium sulfate; Oxidative colitis; Mitochondria; Hyperplasia; N-acetylcysteine
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2012.06.014

The effect of N-acetylcysteine (NAC), a pharmacological antioxidant was investigated in a murine model of chronic colitis. Male NMRI mice were given 5% dextran sulfate sodium (DSS) in drinking water for 5 days followed by 10 days of water, three times. Compared to control mice given water, DSS-treated mice displayed severe imbalanced redox status with decreased glutathione and catalase, but increased malondialdehyde, protein carbonyls, nitric oxide and myeloperoxidase levels, at days 35th (active colitis) and 45th (recovery period). It also resulted in mitochondrial dysfunction, mucosal ulcers, mucin-depleted crypts and epithelial cell apoptosis. Crypt abscesses and glandular hyperplasia occurred selectively in distal colon. NAC (150mg/kg) given in drinking water for 45 days along with 3 DSS cycles improved the hallmarks of DSS-colitis. Interestingly, the moderate impact of NAC on lipids and proteins oxidation correlated with myeloperoxidase and nitric oxide levels.NAC as a mucoregulator and a thiol restoring agent is protective on oxidative crypt alterations, mucin depletion, epithelial cell hyperplasia and apoptosis. Taken together, our results highlight the role of NAC as a scavenger of phagocytes-derived reactive oxygen species in mice DDS-colitis, suggesting that a long term NAC diet might be beneficial in inflammatory bowel diseases and colorectal cancer.