P029 Azelnidipine, a novel calcium channel blocker, ameliorates severity of colitis in DSS induced colitis in mice possibly by modulating tissue levels of TNF-alpha and IL-6

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Background: Inflammatory mediators play an important role for the development inflammatory bowel disease (IBD). Regulation of this mediators is essential in the treatment of IBD, for which immune suppressants and biologics are used with the risk of suppressing the immune response. Azelnidipine is a novel calcium channel blocker (CCB) introduced for the treatment of hypertension however, growing body of evidence supports that this CCB has some anti-inflammatory properties. The aim of this study was to determine whether Azelnidipine could suppress the inflammation in DSS colitis model in mice

Methods: Six week old mice were randomized into four groups; sham, Azelnidipine control, DSS control and DSS + Azelnidipine. Mice that were exposed to 3% DSS for 7 days developed acute colitis. At the end of experiment period all of the mice were sacrificed, blood sample was taken, whole colon was excised, and distal colon segment of at least 1 cm were resected and cut into half for histopathology examination, determination tissue and serum levels of TNF alpha, VCAM and IL-6 levels.

Results: Serum levels of TNF alpha, VCAM and IL-6 levels were not different between groups (p>0.05) However, tissue levels of TNF alpha (p=0.05) and IL-6 (p<0.05) were significantly different in DSS control group. There is no difference between DSS + Azelnidipine and control or sham groups regarding tissue levels of examined cytokines. Azelnidipine attenuated the histological damage compared to DSS control (p=0.05).

Conclusions: Azelnidipine exerted a beneficial effect in acute DSS induced colitis by modulating the tissue levels of TNF alpha and IL-6. A change in experimental design would yield more valuable effect in chronic colitis model. Modulation of tissue levels of cytokines, not the blood levels, support that Azelnidipine has anti-inflammatory effect at the damaged tissue. We believe this is a noteworthy observation of inflammatory response modulation by a calcium channel blocker in colitis model.

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