The effects of rebamipide, sucralfate, and rifaximin against inflammation and apoptosis in radiation-induced murine intestinal injury

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 re...

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Main Authors: Won Moon, Sangwook Lim, Yeonsoon Jung, Yuk Moon Heo, Seun Ja Park, Moo In Park, Sung Eun Kim, Jae Hyun Kim, Kyoungwon Jung
Format: Article
Language:English
Published: Kosin University College of Medicine 2022-12-01
Series:Kosin Medical Journal
Subjects:
Online Access:http://www.kosinmedj.org/upload/pdf/kmj-22-140.pdf
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author Won Moon
Sangwook Lim
Yeonsoon Jung
Yuk Moon Heo
Seun Ja Park
Moo In Park
Sung Eun Kim
Jae Hyun Kim
Kyoungwon Jung
author_facet Won Moon
Sangwook Lim
Yeonsoon Jung
Yuk Moon Heo
Seun Ja Park
Moo In Park
Sung Eun Kim
Jae Hyun Kim
Kyoungwon Jung
author_sort Won Moon
collection DOAJ
description 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.
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spelling doaj.art-86b8b4716332443abd351961c353b40f2023-03-31T01:32:06ZengKosin University College of MedicineKosin Medical Journal2005-95312586-70242022-12-0137432034110.7180/kmj.22.1401221The effects of rebamipide, sucralfate, and rifaximin against inflammation and apoptosis in radiation-induced murine intestinal injuryWon Moon0Sangwook Lim1Yeonsoon Jung2Yuk Moon Heo3Seun Ja Park4Moo In Park5Sung Eun Kim6Jae Hyun Kim7Kyoungwon Jung8 Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea Department of Radiation Oncology, Kosin University College of Medicine, Busan, Korea Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea Kosin University College of Medicine, Busan, Korea Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea Department of Internal Medicine, Kosin University College of Medicine, Busan, KoreaBackground 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.http://www.kosinmedj.org/upload/pdf/kmj-22-140.pdfintestinesradiationrebamipiderifaximinsucralfate
spellingShingle Won Moon
Sangwook Lim
Yeonsoon Jung
Yuk Moon Heo
Seun Ja Park
Moo In Park
Sung Eun Kim
Jae Hyun Kim
Kyoungwon Jung
The effects of rebamipide, sucralfate, and rifaximin against inflammation and apoptosis in radiation-induced murine intestinal injury
Kosin Medical Journal
intestines
radiation
rebamipide
rifaximin
sucralfate
title The effects of rebamipide, sucralfate, and rifaximin against inflammation and apoptosis in radiation-induced murine intestinal injury
title_full The effects of rebamipide, sucralfate, and rifaximin against inflammation and apoptosis in radiation-induced murine intestinal injury
title_fullStr The effects of rebamipide, sucralfate, and rifaximin against inflammation and apoptosis in radiation-induced murine intestinal injury
title_full_unstemmed The effects of rebamipide, sucralfate, and rifaximin against inflammation and apoptosis in radiation-induced murine intestinal injury
title_short The effects of rebamipide, sucralfate, and rifaximin against inflammation and apoptosis in radiation-induced murine intestinal injury
title_sort effects of rebamipide sucralfate and rifaximin against inflammation and apoptosis in radiation induced murine intestinal injury
topic intestines
radiation
rebamipide
rifaximin
sucralfate
url http://www.kosinmedj.org/upload/pdf/kmj-22-140.pdf
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