P029. Protective effects of N-acetylcysteine on mitochondrial dysfunction, mucin-depleted crypts and epithelial apoptosis in dextran sulfate sodium-induced sub-acute colitis
I. Amrouche-Mekkioui, B. Djerdjouri, University of Sciences and Technology Houari Boumediene, Faculty of Biology, Cellular and Molecular Biology Department, Algiers, Algeria
Inflammatory bowel diseases (IBD) are characterized by a succession of acute inflammatory and remission phases. A crosstalk between the innate immune response, chronic inflammation and overproduction of reactive oxygen species (ROS) increases the risk of IBD-associated colorectal cancer. Deal with this oxidative stress and limitations of current therapies which are associated with significant side effects, it is essential to develop therapeutic strategies using pharmacological antioxidant molecules.
Mice were administrated two cycles of 5% dextran sulfate sodium (DSS) in drinking water with or without 150 mg kg-1 N-acetylcysteine (NAC) a pharmacological antioxidant (Amrouche-Mekkioui et al., Eur J Pharmacol. 2012, 601:209–217). The colons harvested at days 20th (active colitis) and 30th (recovery period) were processed to biochemical and histological analyzes conducted in parallel.
The results showed that compared to control mice given tap water; DSS induced colon shortening and deeply altered mucosal architecture in both proximal and distal colon in active and recovery periods. Proximal colon shows ulcers while distal colon is characterized by bifid and horizontalized crypts, crypt abscesses and mucin-depleted crypts. Colons of DSS-treated mice displayed imbalanced redox status with increased malondialdehyde, protein carbonyls, nitric oxide, myeloperoxidase and epithelial cell apoptosis, and decreased glutathione and catalase levels. Moreover, DSS treatment induced mitochondrial swelling and inhibition of respiration. NAC improved colitis scores through the restoration of glutathione, catalase activity and mitochondrial function but has moderate impact on lipids and proteins oxidation and on myeloperoxidase levels. NAC also improved oxidative crypt alterations, mucin depletion and epithelial cell apoptosis.
NAC has a protective effect in vivo against mitochondrial dependent toxicity related to ROS, cryptic changes and mitochondrial function, in part, by the restoration of the redox status and mucin secretion. Taken together, our results highlight the role of NAC as a scavenger of phagocytes-derived ROS in mice model of sub-acute DSS-colitis, suggesting that NAC diet might be beneficial in inflammatory bowel diseases.