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Effect of Niacin on Inflammation and Angiogenesis in a Murine Model of Ulcerative Colitis.

ABSTRACT: Butyrate and niacin are produced by gut microbiota, however butyrate has received most attention for its effects on colonic health. The present study aimed at exploring the effect of niacin on experimental colitis as well as throwing some light on the ability of niacin to modulate angiogenesis which plays a crucial role of in the pathogenesis of inflammatory bowel disease. Rats were given niacin for 2 weeks. On day 8, colitis was induced by intrarectal administration of iodoacetamide. Rats were sacrificed on day 15 and colonic damage was assessed macroscopically and histologically. Colonic myeloperoxidase (MPO), tumour necrosis factor (TNF)-α, interleukin (IL)-10, vascular endothelial growth factor (VEGF), angiostatin and endostatin levels were determined. Niacin attenuated the severity of colitis as demonstrated by a decrease in weight loss, colonic wet weight and MPO activity. Iodoacetamide-induced rise in the colonic levels of TNF-α, VEGF, angiostatin and endostatin was reversed by niacin. Moreover, niacin normalized IL-10 level in colon. Mepenzolate bromide, a GPR109A receptor blocker, abolished the beneficial effects of niacin on body weight, colon wet weight as well as colonic levels of MPO and VEGF. Therefore, niacin was effective against iodoacetamide-induced colitis through ameliorating pathologic angiogenesis and inflammatory changes in a GPR109A-dependent manner.

SUBMITTER: Salem HA

PROVIDER: S-EPMC5541000 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other

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Project description:Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal cancer, particularly in ulcerative colitis (UC) when the majority of colon epithelial cells may be exposed to inflammation-associated mutagenesis. In addition to mutagenesis generated by oxidative stress, inflammation can induce activation-induced cytidine deaminase (Aicda), a mutator enzyme in the APOBEC family, within colon epithelial cells. This study tested the hypothesis that deletion of the Aicda gene could protect against the development of inflammation-associated colorectal cancers, using a model of UC-like colitis in "T/I" mice deficient in TNF and IL10. Results showed that T/I mice that were additionally Aicda-deficient ("TIA" mice) spontaneously developed moderate to severe UC-like colitis soon after weaning, with histologic features and colon inflammation severity scores similar those in T/I mice. Although the mean survival of TIA mice was decreased compared to T/I mice, multivariable analysis that adjusted for age when neoplasia was ascertained showed a decreased numbers of neoplastic colorectal lesions in TIA mice, with a trend toward decreased incidence of neoplasia. Aicda deficiency increased serum IL1α and slightly decreased IL12p40 and M-CSF, as compared with T/I mice, and led to undetectable levels of IgA, IgG1, IgG2a, IgG2b, and IgG3. Taken together, these studies show that Aicda deficiency can decrease the number of neoplastic lesions but is not sufficient to prevent the risk of inflammation-associated colorectal neoplasia in the setting of severe UC-like inflammation. The TIA model may also be useful for assessing the roles of antibody class-switch recombination deficiency and somatic hypermutation on regulation of microbiota and inflammation in the small intestine and colon, as well as the pathogenesis of colitis associated with hyper-IgM syndrome in humans. Further studies will be required to determine the mechanisms that drive early mortality in TIA mice.

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Effect of Niacin on Inflammation and Angiogenesis in a Murine Model of Ulcerative Colitis.

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