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Therapeutic effect of adenosine on experimentally induced acute ulcerative colitis model in rats.

ABSTRACT: PURPOSE:To examine the therapeutic effect of external adenosine on an acetic acid-induced acute ulcerative colitis model in rats. METHODS:Thirty male mature rats were divided into three groups as control, acute colitis (AC) and AC+adenosine group (AC+AD). AC was induced by rectal administration of 4% acetic acid (AA). 5mg/kg/day adenosine was performed i.p for 4 weeks to AC+AD group. Rectum and colon were excised for microscopic and histopathological histopathologic evaluations, and immunohistochemical analysis of nuclear factor kappa B (NF-kB). Blood samples were collected for biochemical detection of TNF-?, Pentraxin-3 and malondialdehyde (MDA) levels. RESULTS:AC group had generalized hyperemia and hemorrhage with increased macroscopic and histopathological scores compared with control (P <0.0001) while adenosine treatment decreased these scores significantly (P <0.001), with reduced distribution of disrupted epithelium, leukocyte infiltrates, and focal hemorrhage. AC group showed significantly increased immunoexpression of NF-kB in rectum, plasma and tissue levels of TNF-?, plasma Pentraxin-3 and MDA levels (P <0.0001) while adenosine reduced these levels (P < 0.05). CONCLUSION:Adenosine appears to promote healing of colon and rectum exposed to AA-induced AC, suggesting a boosting effect of adenosine on the intestinal immune system to cure ulcerative colitis.

SUBMITTER: Ercan G

PROVIDER: S-EPMC7025795 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Therapeutic effect of adenosine on experimentally induced acute ulcerative colitis model in rats.

Ercan Gulcin G Yigitturk Gurkan G Erbas Oytun O

Acta cirurgica brasileira 20200214 12

<h4>Purpose</h4>To examine the therapeutic effect of external adenosine on an acetic acid-induced acute ulcerative colitis model in rats.<h4>Methods</h4>Thirty male mature rats were divided into three groups as control, acute colitis (AC) and AC+adenosine group (AC+AD). AC was induced by rectal administration of 4% acetic acid (AA). 5mg/kg/day adenosine was performed i.p for 4 weeks to AC+AD group. Rectum and colon were excised for microscopic and histopathological histopathologic evaluations, a ...[more]

PMID: 32074166

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Project description:BackgroundUlcerative colitis is a gut inflammatory disorder due to altered immune response to gut microbiome, with interplay of environmental and genetic factors. TNF-? activates inflammatory response through a cascade of immune responses, augmenting pro-inflammatory mediators and proteases, activating chemotaxis, and infiltration of inflammatory cells, leading to ulceration and haemorrhage through cytotoxic reactive oxygen species. 6-Paradol, a dietary component in several plants belonging to the Zingiberaceae family, has shown anti-inflammatory and antioxidant activities. Current study evaluates the effect of 6-paradol in amelioration of ulcerative colitis in rats for the first time.Methods6-Paradol (95% purity) was obtained from seeds of Aframomum melegueta. Rats were divided randomly into six groups (n?=?8). Group one was administered normal saline; group two was treated with the vehicle only; group three, sulfasalazine 500?mg/kg; and groups four, five, and six, were given 6-paradol (50, 100, 200, respectively) mg/kg orally through gastric gavage for 7?days. Colitis was induced on 4th day by intrarectal administration of 2?ml acetic acid (3%), approximately 3?cm from anal verge. On 8th day, rats were sacrificed, and distal one-third of the colon extending proximally up to 4?cm from anal orifice was taken for biochemical and gross examination. Two centimetres of injured mucosal portion was taken for histopathological investigations. SPSS (ver.26) was used for statistical analysis.ResultsColonic and serum glutathione (GSH) levels decreased, while colonic and serum malondialdehyde (MDA), colonic myeloperoxidase (MPO) activity, serum interleukin-6 (IL-6), serum tumour necrosis factor-? (TNF-?) levels, and colon weight to length ratio were increased significantly in the colitis untreated group compared to normal control. Treatment with 6-paradol considerably improved all these parameters, especially at a dose of 200?mg/kg (p?<?0.001), revealing non-significant differences with sulfasalazine 500?mg/kg and normal control (p?=?0.998). Sulfasalazine and 6-paradol in a dose dependent manner also markedly reversed mucosal oedema, atrophy and inflammation, cryptic damage, haemorrhage, and ulceration. There were non-significant differences between low and medium doses and between medium and high doses of 6-paradol for IL-6 and serum MDA levels.Conclusion6-Paradol demonstrated protection against acetic acid-induced ulcerative colitis, probably by anti-inflammatory and antioxidant actions.

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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Therapeutic effect of adenosine on experimentally induced acute ulcerative colitis model in rats.

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Therapeutic effect of adenosine on experimentally induced acute ulcerative colitis model in rats.

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