We previously found that exogenous GSH enhances mucosal GSH and promotes
lipid hydroperoxide metabolism by rat small intestine (AW, T. Y., and M. W. WIlliams, 1992. Am. J. Physiol. 263:G665-G672). In this study, we have developed an in vivo bile and lymph
fistula rat model to test the hypothesis that biliary GSH is an important
luminal source of GSH. Peroxidized
fish oil was infused into the proximal intestine, and
hydroperoxide accumulation in lumen, mucosa, and lymph was determined. Diversion of bile decreased mucosal GSH and increased
hydroperoxide accumulation in all fractions. Supplementation with GSH, but not with
GSSG, increased tissue GSH and attenuated
hydroperoxide accumulation (50-60%), consistent with enhancement of
hydroperoxide removal by exogenous GSH. Addition of native bile deficient in GSH, but not
cysteine,
cystine, or
GSSG, decreased
luminal and lymph
hydroperoxide levels by 20-30%.
Amino acid supplementation concurrently attenuated
hydroperoxide recoveries in these fractions by 30-40% and increased mucosal GSH by 40%, indicating a role for biliary
amino acids in
hydroperoxide elimination. The effect of
amino acids was abolished by
buthionine sulfoximine, confirming their role in GSH biosynthesis. Collectively, the results demonstrate that bile is a rich source of
reductant for maintaining mucosal GSH to promote intestinal metabolism of
luminal peroxidized
lipids.