Enhancing Parenteral Nutrition Formulations: The Role of Antioxidants and Trace Elements in Reducing Oxidative Stress and Improving Neonatal Liver and Gut Health

Thilini Kumarasinghe
PhD Student 
Department of Biochemistry

Date: March 24, 2025
Time: 1:00 p.m. to 2:00 p.m. 
Room: CSF 1302

Abstract:

Parenteral nutrition (PN) is essential for neonates with extreme prematurity or compromised gastrointestinal function. However, prolonged PN use is associated with liver damage and intestinal atrophy, partly due to oxidative stress from nutrient oxidation during administration. Our research focuses on optimizing PN formulations to mitigate these adverse effects, promoting a smoother transition to enteral feeding and reducing hospital stays.

 In our initial study using a neonatal piglet model, we investigated the effects of supplementing a commercial lipid emulsion (SMOFlipid®) with vitamins E and C. This supplementation significantly reduced hepatic lipid peroxidation, while increasing plasma and liver vitamin E concentrations, indicating enhanced antioxidant protection and potential improvements in liver function. Despite these promising results, no significant changes were observed in superior mesenteric artery blood flow or gut morphology.

 Building on these findings and with additional findings from in vitro work conducted in our lab, our next study aims to test an optimized PN formulation in a piglet model over a 10-day period of PN feeding. We hypothesize that supplementation with vitamins E and C and glutathione (an endogenous antioxidant peptide), along with adjustments in trace elements, specifically higher selenium concentrations, will further reduce oxidative stress markers and sustain improved blood flow to the gut. To test this, we will evaluate liver damage markers, oxidative stress indicators (TBARS, FRAP, FOX assay), and key antioxidant enzymes (glutathione synthase, glutathione peroxidase, superoxide dismutase). Vitamin E and total glutathione concentrations will be measured using established HPLC methods. Additionally, an implanted ultrasonic probe will monitor gut blood flow twice daily, and histological analysis will assess tissue integrity. Stable isotope tracers (L-phenylalanine [Ring-D5], L-tyrosine [Ring-3,5-D2], L-tyrosine [Ring-D4], and L-[ring-D8] phenylalanine) will measure whole-body and tissue-specific protein synthesis rates.

 Through this research, we strive to contribute significantly to the field of neonatal care by providing evidence-based strategies to improve parenteral nutrition formulations. This research not only addresses a critical gap in neonatal nutrition but also has the potential to inform clinical practices and guidelines, thereby enhancing the standard of care for vulnerable neonatal populations.