In Vitro Optimization of Antioxidants on the Peroxidation of Total Parenteral Nutrition for Newborns

Kandeepan Karthigesu
Ph.D Student
Department of Biochemistry

Date: November 6, 2023
Time: 1:00-2:00 p.m.
Room: CSF-1302

Premature, low birth-weight newborns typically have immature gut functions that require additional routes of nutritional support. Intravenous (IV) administration of nutrients is often unavoidable in fulfilling their daily requirement, thus, total parenteral nutrition (TPN) feeding has become essential to the clinical management of such infants. However, TPN solutions have been shown to rapidly generate oxidants because of its elemental admixture with lipid emulsion (LE). Furthermore, exposure to light, oxygen, and neonatal intensive care unit (NICU) temperature further induces the generation of oxidants. Studies have suggested that these chemically altered elemental nutrients in the TPN bag can also result in in vivo oxidant generation that impacts newborn metabolism when infused intravenously. However, we know very little about oxidant load from nutrient interactions in TPN solutions and their impact on the health outcomes of the neonate. We aimed to assess the peroxidation of the commercially available TPN mixtures with increasing levels of antioxidants and decreasing levels of prooxidants and optimizing the environmental conditions. We used in vitro assessment of peroxides using cell culture and LC-MS/MS models. As expected, we showed that TPN exposed to light and air for 24 h had higher peroxide levels compared to light- and air-protected TPN. Adding vitamins C or E or selenium, or reducing Zn or Cu did not reduce the peroxide levels of TPN. However, combining both vitamin C and E or increasing levels of glutathione disulfide (GSSG) reduced peroxides significantly compared to standard TPN. To further examine lipid peroxidation, THP-1 human monocytes incubated with 1% lipid emulsion and 10% all-in-one- (AIO)-TPN (16 h; 37°C) had higher TBARS levels compared to cells with no LE or AIO-TPN. We also found that antioxidants added to TPN significantly reduced the TBARS levels compared to standard TPN. The LC-MS/MS model revealed that standard TPN or light-exposed TPN generated fatty acid oxidation products. Overall, this study suggests adding additional vitamins C at 2.3 mM and E at 88.8 µM, selenium at 0.24 µM, and GSSG at 40 µM concentrations can reduce oxidant levels.