RGD Reference Report - BTZO-15, an ARE-activator, ameliorates DSS- and TNBS-induced colitis in rats. - Rat Genome Database

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BTZO-15, an ARE-activator, ameliorates DSS- and TNBS-induced colitis in rats.

Authors: Yukitake, H  Kimura, H  Suzuki, H  Tajima, Y  Sato, Y  Imaeda, T  Kajino, M  Takizawa, M 
Citation: Yukitake H, etal., PLoS One. 2011;6(8):e23256. doi: 10.1371/journal.pone.0023256. Epub 2011 Aug 10.
RGD ID: 10766442
Pubmed: PMID:21853095   (View Abstract at PubMed)
PMCID: PMC3154330   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0023256   (Journal Full-text)

Inflammatory bowel disease (IBD) is a group of chronic inflammatory disorders that are primarily represented by ulcerative colitis and Crohn's disease. The etiology of IBD is not well understood; however, oxidative stress is considered a potential etiological and/or triggering factor for IBD. We have recently reported the identification of BTZO-1, an activator of antioxidant response element (ARE)-mediated gene expression, which protects cardiomyocytes from oxidative stress-induced insults. Here we describe the potential of BTZO-15, an active BTZO-1 derivative for ARE-activation with a favorable ADME-Tox profile, for the treatment of IBD. BTZO-15 induced expression of heme oxygenase-1 (HO-1), an ARE-regulated cytoprotective protein, and inhibited NO-induced cell death in IEC-18 cells. Large intestine shortening, rectum weight gain, diarrhea, intestinal bleeding, and an increase in rectal myeloperoxidase (MPO) activity were observed in a dextran sulfate sodium (DSS)-induced colitis rat model. Oral administration of BTZO-15 induced HO-1 expression in the rectum and attenuated DSS-induced changes. Furthermore BTZO-15 reduced the ulcerated area and rectal MPO activity in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis rats without affecting rectal TNF-alpha levels. These results suggest that BTZO-15 is a promising compound for a novel IBD therapeutic drug with ARE activation properties.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
colitis treatmentISOHmox1 (Rattus norvegicus)10766442; 10766442 RGD 
colitis treatmentIEP 10766442 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hmox1  (heme oxygenase 1)

Genes (Mus musculus)
Hmox1  (heme oxygenase 1)

Genes (Homo sapiens)
HMOX1  (heme oxygenase 1)


Additional Information