P104 Rebamipide, sucralfate, and rifaximin have the suppressive effects on radiation-induced inflammation in the intestine of mouse

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Abstract

Background: Radiotherapy for malignant abdominopelvic disease results in radiation-induced enterocolitis. However, there is no well-established preventive strategy. The aim is to evaluate the suppressive effect of rebamipide, sucralfate and rifaximin on ionizing radiation (IR)-induced acute inflammation and apoptosis in the intestine of mouse.

Methods: Thirty ICR mice were divided into (1) a vehicle-treated control group before sham IR, (2) a vehicle-treated group before IR, and (3–5) rebamipide, sucralfate or rifaximin-treated groups before IR. The intestine was resected at 4 hours after 4 Gy IR to the abdominopelvis. Pro-/anti-inflammatory and pro-/anti-apoptotic factors were investigated.

Results: NAMPT was down-regulated after IR, which was attenuated by rebamipide, sucralfate and rifaximin (p<0.05). Activation of NF-κB and phosphorylation of MAPKs were induced by IR, which were suppressed by rebamipide, sucralfate, and rifaximin (p<0.05). TNF-α, IL-1β, and IL-6 were increased by IR, while attenuated by rebamipide, sucralfate, and rifaximin down to similar level of control group (p<0.05). The iNOS, COX-2 and PGE2 were significantly induced by IR, which were attenuated by rebamipide, sucralfate, and rifaximin (p<0.05). ICAM-1 was corresponded to above mentioned results. [Ca2+] oscillation was increased by IR, which was attenuated by rebamipide, sucralfate, and rifaximin. Proapoptotic gene (Bax, c-Myc) and antiapoptotic gene (Bcl-2, Bcl-xL) expressions were potently suppressed and induced, respectively, by rebamipide, sucralfate, and rifaximin. The release of cytochrome C was increased by IR, while it was attenuated by rebamipide, sucralfate, and rifaximin (p<0.05). Caspase 3 and caspase 7 were also elevated by IR compared to control group, however, they showed decline by rebamipide, sucralfate, and rifaximin (p<0.05).

Conclusions: This study demonstrated that rebamipide, sucralfate, and rifaximin have the suppressive effects on IR-induced acute inflammation and apoptosis in the intestine of mouse. Rebamipide, sucralfate, and rifaximin may have beneficial effects in preventing acute radiation-induced enterocolitis.

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