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P461. Influence of melatonin on the course of ulcerative colitis

A. Dorofeyev, O. Rassokhina, National Medical University, Chair Internal Medicine #2, Donetsk, Ukraine

Background

Melatonin is one of the essential hormones, which regulates circadian rhythms, has anticancerogenic, antioxidant, immunomodulating effects, inhibits proliferation of the colon mucosa, influents on microbiota, modifies peristaltics and the gut transit. A significant amount of extrapineal melatonin is produced in the large intestine. The role of the melatonin in pathogenesis of ulcerative colitis (UC) is still unclear. Administration of melatonin can be one of the new therapeutic options in the treatment of UC.

Methods

Double-blind, multicenter, randomized clinical study in 62 patients with mild and moderate UC in acute phase of disease was performed. Clinical severity of UC was based on Mayo score assessment. Endoscopic (EI) and histological (HI) indexes were evaluated. Bioptates of the colon mucosa were stained by haematoxylin-eosin, alcian blue at pH 1.0 and 2.5, PAS-reaction. Melatonin containing EC-cells were identified by Sevka's method. Immunohistochemistry was performed using monoclonal mouse antibodies raised against the mucins (Muc2, Muc3, Muc4), trefoil factor-3 (TFF3) and CD3, CD20, CD34, CD68. All patients received standard treatment of UC (5-ASA, topical steroids) during 30 days. 32 patients were treated with melatonin (2 mg per day orally) in addition to the base therapy (1st group). 30 patients who didn't receive melatonin were considered as a 2nd group.

Results

Before the therapy total Mayo index in all UC patients's group consisted 7.6+0.9 score points. The severity of UC correlated with the extensive of inflammation in the large intestine. The level of staining of Muc2 and Muc3 in all patients with UC was low, up to its complete absence (59.2% and 53.1% cases, p = 0.05). Muc4 and TFF3 had high and medium staining intensity. Low quantity of EC-cells in the colon mucosa was found. After the treatment the most pronounced improvement was found in patients who received melatonin in addition to the standard treatment. Clinical remission was achieved earlier in the 1st group (day 12.2+4.1) with Mayo index 1.9+0.5 score points in contrast to the 2nd group: remission on 18.3+7.2 days, index Mayo 2.7+0.8 (p = 0.05). The significant evidence of mucosal healing was mentioned in patients with melatonin: EI 1.1+0.5, HI 1.8+0.8, which were accompanied with increasing of Muc2 and Muc3 production (up to 75% cases), quantity of EC-cells, changes of CD3, CD20, CD34, CD68 in the colon mucosa.

Conclusion

Melatonin application in addition to the standard treatment of UC was more effective than standard therapy alone. Melatonin showed significant improvement in the course of disease, earlier achievement of remission phase, evidence of deep histological remission in patients with UC.