1. Curcumin Inhibits 5-Fluorouracil-induced Up-regulation of CXCL1 and CXCL2 of the Colon Associated with Attenuation of Diarrhoea Development
- Author
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Taiki Saito, Hiroyasu Sakai, Aya Oguchi, Fumiaki Sato, Shoko Tabata, Ken Sato, Tetsuro Yumoto, Minoru Narita, Miyabi Yaegashi, Minami Kimura, and Yuki Kai
- Subjects
Diarrhea ,Male ,0301 basic medicine ,Antimetabolites, Antineoplastic ,Chemokine ,Curcumin ,Chemokine CXCL1 ,animal diseases ,Chemokine CXCL2 ,Pharmacology ,Toxicology ,Severity of Illness Index ,Antioxidants ,Descending colon ,Tissue Culture Techniques ,03 medical and health sciences ,chemistry.chemical_compound ,Intestinal mucosa ,medicine ,Animals ,Cyclic adenosine monophosphate ,Enzyme Inhibitors ,Intestinal Mucosa ,biology ,Chemistry ,Anti-Inflammatory Agents, Non-Steroidal ,NF-kappa B ,General Medicine ,NFKB1 ,Colon, Descending ,Mice, Inbred C57BL ,CXCL1 ,CXCL2 ,030104 developmental biology ,medicine.anatomical_structure ,Gene Expression Regulation ,Dietary Supplements ,biology.protein ,Fluorouracil ,E1A-Associated p300 Protein - Abstract
The compound 5-fluorouracil (5-FU) is used in cancer chemotherapy and is known to cause diarrhoea. We recently reported that chemokine (C-X-C motif) ligand 1 (CXCL1) and neutrophils in the colonic mucosa were markedly increased by the administration of 5-FU in mice. Curcumin has anti-inflammatory, antitumour and antioxidant properties. Therefore, we examined the effect of curcumin on 5-FU-induced diarrhoea development and CXCL1 and CXCL2 up-regulation in the colon. Mice were given 5-FU (50 mg/kg, i.p.) daily for 4 days. Curcumin (100 or 300 mg/kg, p.o.) was administered on the day before the first administration of 5-FU and administered 30 min. before the administration of 5-FU. Gene expression levels of CXCL1 and CXCL2 in the colon were examined by real-time RT-PCR. Curcumin reduced the 5-FU-induced diarrhoea development. Under this condition, the CXCL1 and CXCL2 gene up-regulated by 5-FU administration was inhibited by curcumin. The gene expression of CXCL1 and CXCL2 was also enhanced by 5-FU application in vitro. The 5-FU-induced up-regulated CXCL1 and CXCL2 gene expressions were inhibited by curcumin, Bay-117082 and bortezomib, nuclear factor kappa B (NF-κB) inhibitors, C646, a p300/cyclic adenosine monophosphate response element-binding protein-histone acetyltransferase (HAT) inhibitor. In conclusion, these findings suggested that curcumin prevented the development of diarrhoea by inhibiting NF-κB and HAT activation.
- Published
- 2016