Curcumin Inhibits 5‐Fluorouracil‐induced Up‐regulation of CXCL 1 and CXCL 2 of the Colon Associated with Attenuation of Diarrhoea Development

• Published in: Basic & clinical pharmacology & toxicology 2016-12, Vol.119 (6), p.540-547
• Main Authors: Sakai, Hiroyasu, Kai, Yuki, Oguchi, Aya, Kimura, Minami, Tabata, Shoko, Yaegashi, Miyabi, Saito, Taiki, Sato, Ken, Sato, Fumiaki, Yumoto, Tetsuro, Narita, Minoru
• Format: Article
• Language: English
• ISSN: 1742-7835; 1742-7843
• DOI: 10.1111/bcpt.12619

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 ( CXCL 1) 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 CXCL 1 and CXCL 2 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 CXCL 1 and CXCL 2 in the colon were examined by real‐time RT ‐ PCR . Curcumin reduced the 5‐ FU ‐induced diarrhoea development. Under this condition, the CXCL 1 and CXCL 2 gene up‐regulated by 5‐ FU administration was inhibited by curcumin. The gene expression of CXCL 1 and CXCL 2 was also enhanced by 5‐ FU application in vitro . The 5‐ FU ‐induced up‐regulated CXCL 1 and CXCL 2 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.