3,3'-Diindolylmethane decreases VCAM-1 expression and alleviates experimental colitis via a BRCA1-dependent antioxidant pathway.

Abstract

Reactive oxygen species (ROS) exhibit a key role in the pathogenesis of inflammatory bowel disease (IBD). 3,3'-Diindolylmethane (DIM) can protect against oxidative stress in a breast cancer susceptibility gene 1 (BRCA1)-dependent manner. The aim of this study was to examine the therapeutic effects of DIM in experimental colitis and investigate the possible mechanisms underlying its effects on intestinal inflammation. The therapeutic effects of DIM were studied in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Pathological markers of colitis severity, antioxidant activity, and ROS generation in colonic tissue were measured. The impact of DIM on ROS-induced endothelial vascular cell adhesion molecule 1 (VCAM-1) expression and leukocyte-endothelial cell interaction was further investigated in cultures of endothelial cells and in the TNBS-induced colitis model. Administration of DIM was demonstrated to attenuate experimental colitis, as judged by pathological indices. DIM could effectively stimulate the expression of BRCA1 in vitro and in vivo and reduce ROS generation, leading to the inhibition of VCAM-1 expression and leukocyte-endothelial cell adhesion, and finally resulted in an alleviation of experimental colitis. DIM has shown anti-IBD activity in animal models by inhibiting ROS-induced VCAM-1 expression and leukocyte recruitment via a BRCA1-dependent antioxidant pathway and thus may offer potential treatments for IBD patients.

• Authors: Zhen Huang, Longsheng Zuo, Zhengping Zhang, Jialin Liu, Jiangning Chen, Lei Dong, Junfeng Zhang
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 50 Issue 2 Pg. 228-36 (Jan 15 2011) ISSN: 1873-4596 [Electronic] United States
• PMID: 21034812 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Inc. All rights reserved.

Chemical References

• Antioxidants
• BRCA1 Protein
• Indoles
• RNA, Messenger
• Reactive Oxygen Species
• Vascular Cell Adhesion Molecule-1
• Trinitrobenzenesulfonic Acid
• 3,3'-diindolylmethane

Topics

• Animals
• Antioxidants (pharmacology)
• BRCA1 Protein (genetics, metabolism)
• Blotting, Western
• Cell Adhesion
• Colitis (chemically induced, metabolism, prevention & control)
• Endothelium, Vascular (cytology, drug effects, metabolism)
• Female
• Fluorescent Antibody Technique
• Humans
• Indoles (pharmacology)
• Leukocytes (cytology, drug effects, metabolism)
• Mice
• Mice, Inbred BALB C
• RNA, Messenger (genetics)
• Reactive Oxygen Species (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Trinitrobenzenesulfonic Acid (toxicity)
• Umbilical Veins (cytology, drug effects, metabolism)
• Vascular Cell Adhesion Molecule-1 (genetics, metabolism)