Interaction between ascorbate and light-exposed riboflavin induces lung remodeling

Light-exposed parenteral multivitamins induce in lungs peroxide-like 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. Three-day-old guinea pigs fitted with an indwelling catheter were assigned to the following intravenous regimens: TPN or MVP +/- photoprotection, H2O2+/- glutathione, MVP +/- metabisulfite, or ascorbic acid +/- riboflavin. Fed animals served as controls. After 4 days, lungs were sampled to determine alveolarization ( intercepts), beta-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 < 0.01) alveolarization index than fed controls, and 3-fold higher ( p < 0.01) apoptotic events. This was prevented by photoprotecting TPN. The effect of multivitamins on the alveolarization index was reproduced ( p < 0.05) by infusion of light-exposed riboflavin in the presence of vitamin C. The alveolarization index correlated (r(2) = 0.35; p < 0.05) with beta-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.