The effects of rebamipide, sucralfate, and rifaximin against inflammation and apoptosis in radiation-induced murine intestinal injury
- Author:
Won MOON
1
;
Sangwook LIM
;
Yeonsoon JUNG
;
Yuk Moon HEO
;
Seun Ja PARK
;
Moo In PARK
;
Sung Eun KIM
;
Jae Hyun KIM
;
Kyoungwon JUNG
Author Information
- Publication Type:Original article
- From:Kosin Medical Journal 2022;37(4):320-341
- CountryRepublic of Korea
- Language:English
-
Abstract:
Background:Radiotherapy improves overall survival in patients with abdominopelvic malignancies. However, the toxic effects of radiation restrict the maximum dose that can be given, and there are no well-established preventive or therapeutic strategies. This study was conducted to evaluate whether rebamipide, sucralfate, and rifaximin have a suppressive effect on acute ionizing radiation (IR)-induced inflammation in the intestines of mice.
Methods:Thirty-six ICR mice were divided into a vehicle-treated group with sham irradiation; a vehicle-treated group with irradiation; rebamipide, sucralfate, or rifaximin-treated groups with irradiation; and a rebamipide-treated group with sham irradiation. The expression of proinflammatory, anti-inflammatory, proapoptotic, and antiapoptotic factors was investigated.
Results:The downregulated expression of nicotinamide phosphoribosyltransferase by IR was attenuated by all drugs (p<0.05). All drugs suppressed the IR-induced activation of NF-κB and phosphorylation of MAPKs (p<0.05) and attenuated the production of TNF-α, IL-1β, and IL-6 in response to IR (p<0.05). The administration of all drugs markedly attenuated IR-induced increases in iNOS, COX-2, and PGE2 (p<0.05), as well as [Ca2+] oscillations that were increased by IR. The expression of proapoptotic genes and antiapoptotic genes was suppressed and induced, respectively, by all drugs. IR treatment increased the release of cytochrome C, which was attenuated by all drugs (p<0.05). All drug treatments resulted in a significant decrease in the expression of caspase-3 and caspase-7 (p<0.05), which were both upregulated following IR treatment.
Conclusions:The administration of rebamipide, sucralfate, or rifaximin prior to radiation therapy may prevent or attenuate acute radiation-induced enterocolitis.
