Induction of enlarged intestinal lymphoid aggregates during acute glutathione depletion in a murine model.
Glutathione is a nonenzymatic antioxidant synthesized by most animal cells and is depleted in inflammatory bowel disease. The effects of glutathione depletion on intestinal histology and inhibitory neurochemicals was examined in a mouse model. Glutathione depletion in A/J mice involved inhibition of gamma-glutamylcysteine synthetase using L-buthionine-(S,R)-sulfoximine (BSO) for 10 days. Ileum and colon were obtained from saline-control mice, BSO-treated mice, and BSO-treated mice receiving ascorbate or glutathione monoethylester. Glutathione, lipid peroxides, and nicotineamide adenine dinucleotide phosphate diaphorase activity were measured by colorimetric assays. Vasoactive intestinal peptide was measured by radioimmunoassay. Glutathione depletion induced enlargement of mucosal-submucosal lymphoid aggregates without germinal centers in ileum and colon. These aggregates were prevented by supplementation with glutathione monoethylester but not ascorbate. Tissue levels of inhibitory neurochemicals were unchanged. Depletion of glutathione appears to induce enlarged lymphoid aggregates by recruitment of lymphocytes from the peripheral circulation. A component of the inflammation that develops in inflammatory bowel disease could be related to depletion of tissue levels of glutathione.
Koch
T R
TR
Section of Gastroenterology, LA Johnson VA Medical Center and West Virginia University, Morgantown 26506-9161, USA.
Yuan
L X
LX
Fink
J G
JG
Petro
A
A
Opara
E C
EC
D000818:Animals; D004195:Disease Models, Animal; D005978:Glutathione / Q000502:physiology*; D006984:Hypertrophy; D015212:Inflammatory Bowel Diseases / Q000473:pathology; D008221:Lymphoid Tissue / Q000473:pathology*; D051379:Mice; D008805:Mice, Inbred A; D018384:Oxidative Stress / Q000502:physiology*
D005978:Glutathione