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Irsogladine Maleate, a Gastric Mucosal Protectant, Suppresses Intestinal Polyp Development in Apc-mutant Mice

Irsogladine Maleate, a Gastric Mucosal Protectant, Suppresses Intestinal Polyp Development in Apc-mutant Mice

Wakana Onuma, Susumu Tomono, Shinngo Miyamoto, Gen Fujii, Takahiro Hamoya, Kyoko Fujimoto, Noriyuki Miyoshi, Fumio Fukai, Keiji Wakabayashi, Michihiro Mutoh

Oncotarget. 2016 Feb 23;7(8):8640-52.

PMID: 26840084

Abstract:

This study aimed to identify gastric mucosal protectants that suppress intestinal tumorigenesis in a mouse model. We chose six gastric mucosal protectants (ecabet sodium hydrate, irsogladine maleate, rebamipide, sofalcone, teprenone and troxipide) and examined their effects on the activity of oxidative stress-related transcriptional factors, including AP-1, NF-jB, NRF2, p53 and STAT3, in Caco-2 cells using a luciferase reporter gene assay. Among the six protectants, irsogladine maleate clearly inhibited NF-jB and AP-1 transcriptional activity. Furthermore, the chemopreventive property of irsogladine maleate was examined in a Min mouse model of familial adenomatous polyposis. Treatment with irsogladine maleate at doses of 5 and 50 ppm significantly reduced the number of intestinal polyps to 69% and 66% of the untreated control value, respectively. In these polyps, mRNA levels of the downstream targets of NF-jB, such as IL-1β and IL-6, were decreased by irsogladine maleate treatment. Moreover, the levels of oxidative stress-related markers, reactive carbonyl species, in the livers of Min mice were clearly decreased following the administration of irsogladine maleate. This study demonstrated that irsogladine maleate suppresses intestinal polyp formation in Min mice partly through the NF-jB signaling pathway, thus reducing oxidative stress.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
ALP90098047	Rebamipide hydrate		90098-04-7 (anhydrous)	Price
AP84504698	Irsogladine maleate		84504-69-8	Price

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