title: Stimulation of colonic mucosal growth associated with oxidized redox status in rats.
abstract: 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.
authors.affiliation: General Clinical Research Center, Emory University Hospital, 1364 Clifton Road, Atlanta, GA 30322, USA.
authors.forename: Junqiang
authors.initials: J
authors.lastname: Tian
authors.forename: Naohiro
authors.initials: N
authors.lastname: Washizawa
authors.forename: Li H
authors.initials: LH
authors.lastname: Gu
authors.forename: Marc S
authors.initials: MS
authors.lastname: Levin
authors.forename: Lihua
authors.initials: L
authors.lastname: Wang
authors.forename: Deborah C
authors.initials: DC
authors.lastname: Rubin
authors.forename: Simon
authors.initials: S
authors.lastname: Mwangi
authors.forename: Shanthi
authors.initials: S
authors.lastname: Srinivasan
authors.forename: Yuhao
authors.initials: Y
authors.lastname: Gao
authors.forename: Dean P
authors.initials: DP
authors.lastname: Jones
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Ziegler
mesh_terms: D000818:Animals; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D003106:Colon / Q000166:cytology* / Q000601:surgery; D003545:Cysteine / Q000032:analysis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005978:Glutathione / Q000032:analysis / Q000378:metabolism; D019803:Glutathione Disulfide / Q000032:analysis / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000254:growth & development*; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004791:Enzyme Inhibitors; D019328:Buthionine Sulfoximine; D005978:Glutathione; D003545:Cysteine; D019803:Glutathione Disulfide