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

Moon W., Park S.J., Kim J.H., Park M.I., Kim S.E., Jung K.W.

Kosin University College of Medicine, Department of Internal Medicine, Busan, South Korea

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).

Conclusion

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.