Tr. Koch et al., Induction of enlarged intestinal lymphoid aggregates during acute glutathione depletion in a murine model, DIG DIS SCI, 45(11), 2000, pp. 2115-2121
Glutathione is a nonenzymatic antioxidant synthesized by most animal cells
and is depleted in inflammatory bowel disease. The effects of glutathione d
epletion 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 (BS
O) for 10 days. Ileum and colon were obtained from saline-control mice, BSO
-treated mice, and BSO-treated mice receiving ascorbate or glutathione mono
ethylester. Glutathione, lipid peroxides, and nicotineamide adenine dinucle
otide phosphate diaphorase activity were measured by colorimetric assays. V
asoactive intestinal peptide was measured by radioimmunoassay, Glutathione
depletion induced enlargement of mucosal-submucosal lymphoid aggregates wit
hout germinal centers in ileum and colon. These aggregates were prevented b
y supplementation with glutathione monoethylester but not ascorbate. Tissue
levels of inhibitory neurochemicals were unchanged. Depletion of glutathio
ne appears to induce enlarged lymphoid aggregates by recruitment of lymphoc
ytes from the peripheral circulation. A component of the inflammation that
develops in inflammatory bowel disease could be related to depletion of tis
sue levels of glutathione.