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GSH is required to maintain gut intracellular cysteine redox status after intestinal surgery in rats
Author(s) -
Tian Junqiang,
Gu Li H,
Jones Dean P,
Ziegler Thomas R
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a146-d
Subject(s) - glutathione , chemistry , glutathione disulfide , oxidative stress , ileum , buthionine sulfoximine , cysteine , biochemistry , cystine , intestinal mucosa , thiol , redox , homeostasis , in vivo , endocrinology , medicine , biology , enzyme , organic chemistry , microbiology and biotechnology
BACKGROUND Glutathione (GSH) and cysteine (Cys) are major low molecular thiols that maintain cellular and plasma redox balance. Available data suggest that GSH may also be important in maintaining Cys homeostasis in vivo . Using buthionine sulfoximine (BSO), a specific rate‐limiting inhibitor of GSH synthesis, to deplete tissue and plasma GSH, we investigated regulation of Cys concentration and redox status by GSH in a rat model of intestinal surgery. METHODS Adult rats underwent laparotomy, jejunal transection and anastomosis, with (n = 6) or without (n = 7) administration of BSO from day 4 until animal sacrifice 7 days after operation. BSO‐treated and control rats were pair‐fed. We measured mucosal and plasma thiol status [GSH, glutathione disulfide (GSSG), Cys and cystine (CySS) levels and redox potential (E h )] and gut free malondialdehyde (MDA), an index of lipid peroxidation. RESULTS BSO markedly decreased ileal, colonic and plasma GSH and GSSG concentrations. Although Cys is a substrate for GSH synthesis (blocked by BSO), mucosal Cys was paradoxically depleted in BSO‐treated rats [−32% in ileum (P = 0.06), −68% (P < 0.05) in colon], suggesting impaired cellular cyst(e)ine uptake. Such thiol depletion resulted in oxidative stress, indicated by oxidation of ileal and colonic GSH/GSSG and Cys/CySS E h , and increased MDA content. In contrast to decreased gut mucosal Cys and CySS, BSO induced a concomitant increase in plasma Cys (+98%, P < 0.05) and CySS (+28%, P < 0.05), indicating impaired tissue extraction from blood. CONCLUSIONS GSH is required to maintain Cys redox status in gut mucosa in rats subjected to major abdominal surgery. Gut mucosal oxidative stress induced by GSH depletion may be exacerbated by impaired GSH dependent Cys uptake from blood in this model. (NIH: R01 DK55850)