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Am J Physiol Regul Integr Comp Physiol 292: R1081-R1091, 2007. First published November 9, 2006; doi:10.1152/ajpregu.00050.2006
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APPETITE, OBESITY, DIGESTION, AND METABOLISM

Stimulation of colonic mucosal growth associated with oxidized redox status in rats

¹Nutrition and Health Science Program, Graduate School of Arts and Science, Emory University, Atlanta; ²Department of Medicine and ³Center for Clinical and Molecular Nutrition, Emory University School of Medicine, Atlanta, Georgia; ⁴Department of Surgery, Toho University School of Medicine, Tokyo, Japan; and ⁵Department of Medicine, Washington University School of Medicine, St. Louis, Missouri

Submitted 19 January 2006 ; accepted in final form 27 October 2006

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., glutathione (GSH)/glutathione disulfide (GSSG) and cysteine (Cys)/cystine (CySS) redox]. We investigated the effects of SBR and alterations in redox on colonic growth indexes in rats after either small bowel transection (TX) or 80% midjejunoileal resection (RX). Rats were pair fed ± blockade of endogenous GSH synthesis with buthionine sulfoximine (BSO). Indexes of colonic growth, proliferation, and apoptosis and GSH/GSSG and Cys/CySS redox potentials (E_h) were determined. RX significantly increased colonic crypt depth, number of cells per 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 E_h. BSO did not alter colonic crypt cell apoptosis but significantly increased all colonic mucosal growth indexes (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 E_h, 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.

cysteine; colon; glutathione; intestine; short bowel syndrome