CPT-11-Induced Delayed Diarrhea Develops via Reduced Aquaporin-3 Expression in the Colon

Autor: Ryoya Sakurai, Kiyoshi Sugiyama, Yukari Matsunaga, Yuta Murakami, Moe Minami, Risako Kon, Yoshiaki Machida, Hiroshi Kimura, Rei Tomimoto, Nobutomo Ikarashi, Tetsuya Fujikawa, Saki Kato, Yuika Tsubota
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
endocrine system diseases
diarrhea
Gene Expression
Nitric Oxide Synthase Type II
Pharmacology
lcsh:Chemistry
Feces
Mice
0302 clinical medicine
CPT-11
Medicine
heterocyclic compounds
lcsh:QH301-705.5
Spectroscopy
General Medicine
Computer Science Applications
Diarrhea
Aquaporin 3
030220 oncology & carcinogenesis
Cytokines
medicine.symptom
medicine.drug
endocrine system
Cell Survival
Crypt
Inflammation
Aquaporins
Irinotecan
Catalysis
Article
Proinflammatory cytokine
Inorganic Chemistry
03 medical and health sciences
Animals
Physical and Theoretical Chemistry
Rats
Wistar
Adverse effect
Molecular Biology
neoplasms
Aquaporin 4
Water transport
colon
business.industry
Organic Chemistry
aquaporin
inflammation
digestive system diseases
Rats
030104 developmental biology
RAW 264.7 Cells
lcsh:Biology (General)
lcsh:QD1-999
Celecoxib
Cyclooxygenase 2
Camptothecin
business
Zdroj: International Journal of Molecular Sciences, Vol 19, Iss 1, p 170 (2018)
International Journal of Molecular Sciences
International Journal of Molecular Sciences; Volume 19; Issue 1; Pages: 170
ISSN: 1422-0067
Popis: While irinotecan (CPT-11) has a potent anti-cancer effect, it also causes serious diarrhea as an adverse reaction. In this study, we analyzed the pathogenic mechanism of CPT-11-induced delayed diarrhea by focusing on water channel aquaporin-3 (AQP3) in the colon. When rats received CPT-11, the expression level of AQP3 was reduced during severe diarrhea. It was found that the expression levels of inflammatory cytokines and the loss of crypt cells were increased in the colon when CPT-11 was administered. When celecoxib, an anti-inflammatory drug, was concomitantly administered, both the diarrhea and the reduced expression of AQP3 induced by CPT-11 were suppressed. The inflammation in the rat colon during diarrhea was caused via activated macrophage by CPT-11. These results showed that when CPT-11 is administered, the expression level of AQP3 in the colon is reduced, resulting in delayed diarrhea by preventing water transport from the intestinal tract. It was also suggested that the reduced expression of AQP3 might be due to the inflammation that occurs following the loss of colonic crypt cells and to the damage caused by the direct activation of macrophages by CPT-11. Therefore, it was considered that anti-inflammatory drugs that suppress the reduction of AQP3 expression could prevent CPT-11-induced delayed diarrhea.
Databáze: OpenAIRE
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