Submitted on January 19, 2006
Accepted on October 27, 2006
Stimulation of colonic mucosal growth associated with oxidized redox status in rats
Junqiang Tian1, Naohiro Washizawa2, Li H Gu2, Marc S. Levin3, Lihua Wang4, Deborah C. Rubin5, Simon Mwangi2, Shanthi Srinivasan6, Yuhao Gao2, Dean P. Jones7, and Thomas R Ziegler7*
1 Nutrition and Health Science Program, EMORY UNIVERSITY, ATLANTA, Georgia, United States
2 Medicine, Emory University School of Medicine, Atlanta, Georgia, United States
3 Medicine, Washington University, St Louis, Missouri, United States
4 Medicine, Washington University School of Medicine, St Louis, Missouri, United States
5 Department of Medicine, Washington University School of Medicine, United States
6 Medicine, Emory University, Atlanta, Georgia, United States
7 Nutrition and Health Science Program, Graduate School of Arts and Science, Medicine, and Molecular Nutrition, Emory University, Atlanta, Georgia, United States
* To whom correspondence should be addressed. E-mail: tzieg01{at}emory.edu.
Limited data in animal models suggest that colonic mucosa undergoes adaptive growth following massive small bowel resection (SBR). In vitro data suggest that intestinal cell growth is regulated by reactive oxygen species and redox couples [e.g. GSH/GSSG and cysteine (Cys)/cystine (CySS) redox]. We investigated the effects of SBR and alterations in redox on colonic growth indices in rats after either small bowel transection (TX) or 80% mid-jejunoileal resection (RX). Rats were pair-fed ± blockade of endogenous GSH synthesis with buthionine-sulfoximine (BSO). Indices of colonic growth, proliferation, and apoptosis, and GSH/GSSG and Cys/CySS redox potentials (Eh) were determined. RX significantly increased colonic crypt depth, number of cells/crypt, and epithelial cell proliferation [crypt cell bromodeoxyuridine (BrdU) incorporation]. Administration of BSO markedly decreased colonic mucosal GSH, GSSG, and Cys concentrations in both TX and RX groups, with a resultant oxidation of GSH/GSSG and Cys/CySS redox potentials (Eh). BSO did not alter colonic crypt cell apoptosis, but significantly increased all colonic mucosal growth indices (crypt depth, cells/crypt, and BrdU incorporation) in both TX and RX groups in a time and dose dependent manner. BSO significantly decreased plasma GSH and GSSG, oxidized GSH/GSSG Eh and increased plasma Cys and CySS concentrations. Collectively, these data provide in vivo evidence indicating that oxidized colonic mucosal redox status stimulates colonic mucosal growth in rats. The data also suggest that GSH is required to maintain normal colonic and plasma Cys/CySS homeostasis in these animal models.
