The effect of glutathione supplementation on intestinal morphology and liver antioxidant status in parenterally fed piglets

Abstract

Total parenteral nutrition (TPN) causes deleterious changes to the gastrointestinal tract (GIT), in part related to the decrease in blood supply that occurs without enteral stimuli. Nitric oxide (NO) regulates blood flow, but in situations of oxidative stress, as with the delivery of oxidized nutrients in TPN, it can react with superoxide and thus limit its function as a vasodilator. We hypothesized that supplementing the antioxidant glutathione to PN would protect NO’s function as a vasodilator, leading to greater blood flow to the GIT. Piglets (8-12 days old) underwent surgery and were randomized to one of three treatment groups for 7 days: control TPN (PN, n=10), control TPN diet with 10 μM glutathione disulfide (GSSG, n=9), or the control TPN diet delivered enterally (EN, n=10). Blood flow (p<0.0001), mucosa weight (p<0.01) and crypt cell proliferation (p<0.01) were higher in the EN compared to both parenterally fed groups. Interestingly, villus height was greater in EN versus PN (p<0.01) but not different from GSSG; liver weight in the GSSG was similar to EN, while PN had a higher liver weight, typical of TPN feeding. The parenteral groups (PN and GSSG) had greater liver antioxidant capacity and less liver lipid peroxidation than EN. These data suggest that glutathione supplementation to TPN delays the changes in intestinal morphology and the route of feeding has a greater effect on antioxidant status than glutathione supplementation in TPN.