The effect of antioxidant supplementation in TPN on the gastrointestinal tract of neonatal piglets.

The use of total parenteral nutrition (TPN) to treat premature infants causes detrimental changes to the structure and function of the gastrointestinal tract (GIT). This is related to the decrease in blood flow when there is no enteral stimulation, as is the case with TPN. Nitric oxide (NO) is important for the regulation of blood flow, but in situations of oxidative stress, it can react with superoxide to form peroxynitrite (ONOO-), which limits its function as a vasodilator. In addition, TPN increases oxidative stress in premature neonates due to the delivery of oxidized nutrients formed in the diet. The endogenous glutathione antioxidant system in preterm newborns is limited due to developmental immaturity and inadequate availability of the precursor cysteine in TPN. We hypothesize that glutathione supplementation to TPN will spare NO, allowing it to function as a vasodilator and thus increasing blood flood to the GIT. Piglets (8-12 days old) underwent a surgery to implant venous catheters and an ultrasonic probe around the superior mesenteric artery to measure blood flow; a gastric catheter was implanted in an enterally-fed control group to determine the effects of route of feeding on oxidative stress. One of three treatments was fed for 7 days: control TPN (C-TPN, n=10), or the same TPN diet with 10 µM glutathione disulfide (GSSG-TPN, n=9), or the control TPN diet delivered enterally (EN, n=10). To date, we report that blood flow (p<0.0001), mucosa weight (p<0.01) and cell proliferation in the gut (p=0.0019) were higher in the EN compared to the C-TPN group, while no differences were observed between C-TPN and GSSG-TPN groups. Ongoing work should elucidate the impact of adding glutathione to TPN by evaluating glutathione status and markers of oxidative stress in the gut, liver and lungs.