Light-exposed parenteral multivitamins induce in lungs peroxidelike oxidant responses as well as the initiation of fibrosis. We hypothesized that peroxides generated in light-exposed total parenteral nutrition (TPN) affect lung remodeling. The objective was to assess the specific roles of peroxides, multivitamin preparation (MVP), and light exposure on lung remodeling during TPN. Threeday-old guinea pigs fitted with an indwelling catheter were assigned to the following intravenous regimens: TPN or MVP Ϯ photoprotection, H 2 O 2 Ϯ glutathione, MVP Ϯ metabisulfite, or ascorbic acid Ϯ riboflavin. Fed animals served as controls. After 4 days, lungs were sampled to determine alveolarization (intercepts), -actin mRNA (protection assay), and apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labeling). Data were analyzed by analysis of variance. The infusion of light-exposed multivitamins induced a 20% lower (p Ͻ 0.01) alveolarization index than fed controls, and 3-fold higher (p Ͻ 0.01) apoptotic events. This was prevented by photoprotecting TPN. The effect of multivitamins on the alveolarization index was reproduced (p Ͻ 0.05) by infusion of light-exposed riboflavin in the presence of vitamin C. The alveolarization index correlated (r 2 ϭ 0.35; p Ͻ 0.05) with -actin mRNA, suggesting alveolar disruption. Antiperoxides conferred no protection against decreased alveolarization. Lung remodeling induced by exposure of TPN to ambient light is not due to a direct effect of infused peroxides but rather to an interaction between vitamin C and peroxides generated by the exposure of riboflavin to light. It is speculated that this interaction may play a role in the development of chronic lung disease of premature infants who receive TPN and have immature antioxidant defenses.
Early O2 supplement and PN have additive effects that were associated with prolonged oxidative stress and increased risk of BPD. Strategies targeting judicious use of O2 and decreasing the duration or developing a safer formulation of PN can be targeted to decrease BPD.
Photooxidation of multivitamin solutions results in the generation of peroxides. Because peroxides are associated with hepatic steatosis and fibrosis as well as cholestasis, we questioned whether multivitamins are implicated in hepatic complications of parenteral nutrition. Guinea pig pups were assigned to groups receiving intravenously either total parenteral nutrition, photo-protected or not, or a control solution (5% dextrose + 0.45% NaCl) supplemented with either a) multivitamins; b) photo-protected multivitamins; c) multivitamins without riboflavin; or d) peroxides (H(2)O(2), tert-butylhydroperoxide). After 4 d, liver was sampled for histology and isoprostane-F(2alpha) levels, a marker of radical attack. Multivitamins as well as total parenteral nutrition were associated with steatosis (scored 0-4), the severity of which was reduced (p < 0.05) by photo protection. Although H(2)O(2) is the major peroxide contaminating multivitamins, it did not induce steatosis scores different than the controls. Compared with controls, hepatic isoprostane-F(2alpha) content increased in animals infused with H(2)O(2) (p < 0.05), but not in those infused with Multi-12 pediatric multivitamins or total parenteral nutrition. Results suggest that peroxides and/or free radicals are not mediators of the induction of steatosis observed with infusion of photo-exposed multivitamins, as there was no correspondence between histologic findings and hepatic levels of isoprostanes. It is suspected that a component of the multivitamin solution becomes hepato-toxic after photo-exposure, as indicated by the protective effect observed when withdrawing riboflavin. Photo-oxidation of multivitamins might be the common link between reports involving amino acids, lipids, and light exposure in the ethiology of hepatic complications of parenteral nutrition.
Background: When solutions of multivitamin preparations (MVPs) are exposed to light, H 2 O 2 as well as organic peroxides are generated and the concentration of vitamin C decreases. The aim of this study was to determine, using mass spectrometry, whether the generation of oxidative byproducts of vitamin C, such as dehydroascorbate (DHA) and 2,3-diketogulonic acid (DKG), accounted for the reported decrease in ascorbic acid in MVPs exposed to light.
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