Immunoregulatory Mechanisms Underlying Prevention of Colitis-Associated Colorectal Cancer by Probiotic Bacteria

Background: Inflammatory bowel disease (IBD) increases the risk of colorectal cancer. Probiotic bacteria produce immunoregulatory metabolites in vitro such as conjugated linoleic acid (CLA), a polyunsaturated fatty acid with potent anticarcinogenic effects. This study aimed to investigate the cellular and molecular mechanisms underlying the efficacy of probiotic bacteria in mouse models of cancer. Methodology/Principal Findings: The immune modulatory mechanisms of VSL#3 probiotic bacteria and CLA were investigated in mouse models of inflammation-driven colorectal cancer. Colonic specimens were collected for histopathology, gene expression and flow cytometry analyses. Immune cell subsets in the mesenteric lymph nodes (MLN), spleen and colonic lamina propria lymphocytes (LPL) were phenotypically and functionally characterized. Mice treated with CLA or VSL#3 recovered faster from the acute inflammatory phase of disease and had lower disease severity in the chronic, tumor-bearing phase of disease. Adenoma and adenocarcinoma formation was also diminished by both treatments. VSL#3 increased the mRNA expression of TNF-a, angiostatin and PPAR c whereas CLA decreased COX-2 levels. Moreover, VSL#3-treated mice had increased IL-17 expression in MLN CD4+ T cells and accumulation of Treg LPL and memory CD4+ T cells. Conclusions/Significance: Both CLA and VSL#3 suppressed colon carcinogenesis, although VSL#3 showed greater anticarcinogeni

N-acetylcysteine expresses powerful anti-inflammatory and antioxidant activities resulting in complete improvement of acetic acid-induced colitis in rats

High free radical production, low antioxidant capacity and excessive inflammation are well known features in the pathogenesis of inflammatory bowel disease. N-acetylcysteine (NAC) is a powerful antioxidant and a scavenger of hydroxyl radicals. Recently, NAC has also been shown to have anti-inflammatory activities in tissues. Our study objective was to investigate the effects of NAC on tissue inflammatory activities using an ulcerative colitis model induced by acetic acid (AA) in rats. Wistar rats (n = 32) were divided into four groups. AA-induced colitis was performed in two of the groups while the other two groups were injected with saline intrarectally. One of the AA-induced colitis groups and one of the control groups were administered NAC (500 mg/kg/day) intrarectally, and the other control groups were given saline. After 4 days, colonic changes were evaluated biochemically by measuring proinflammatory cytokines [tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta and IL-6], myeloperoxidase (MPO), malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) levels in tissue homogenates and by histopathological examination. AA caused colonic mucosal injury, whereas NAC administration suppressed these changes in the AA-induced colitis group (p < 0.001). AA-administration resulted in increased TNF-alpha, IL-1 beta, IL-6, MPO and MDA levels, and decreased GSH and SOD levels, whereas NAC reversed these effects (all p < 0.001). In conclusion, the present study proposes that intrarectal NAC therapy has a dual action as an effective anti-inflammatory and an antioxidant, and may be a promising therapeutic option for ulcerative colitis