Interaction between Ascorbate and Light-Exposed Riboflavin Induces Lung Remodeling

Abstract

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.

Ascorbylperoxide from parenteral nutrition induces an increase of redox potential of glutathione and loss of alveoli in newborn guinea pig lungs

“…Despite this negative effect of H 2 O 2 on caspase-3, the activation remained sufficient to induce a decrease in the alveolar number. The effect of ascorbylperoxide on alveolarization index was similar to the values previously reported in studies investigating the effect of parenteral nutrition [14,15]. …”

“…Alveolarization index represents the mean value for each animal of the number of intercepts between a standardized straight-line (1 mm) and histological structures calculated from four different fields of the same lung (200× magnification) [14,15]. …”

“…Light-protection of PN reduces by half the peroxide generation in intravenous solution [10–12], decreases the incidence of BPD [13] and chronic lung diseases [12] in premature infants and prevents the alveolar loss in newborn guinea pigs [14]. An animal study by Lavoie et al [15] reported that an exaggerated apoptosis is associated with the loss of alveoli, independently of the H 2 O 2 level present in PN. This study also described that the loss of alveoli is reproduced by the infusion of a solution containing vitamin C and riboflavin, components found in PN.…”

Characterizing dynamic regulatory programs in mouse lung development and their potential association with tumourigenesis via miRNA-TF-mRNA circuits

“…For mmu04810, Actin cytoskeleton plays a role in human pulmonary artery ECS [55]. For mmu00740, lung remodelling induced by exposure of total parenteral nutrition to ambient light is due to the interaction between vitamin C and peroxides generated by the exposure of riboflavin to light [56]. For mmu04060, the analysis of lung adenocarcinoma tissue specimens have demonstrated that the genes involved in these biological pathways have high rates of over-expression [57].…”

Impact of shielding parenteral nutrition from light on routine monitoring of blood glucose and triglyceride levels in preterm neonates

“…Peroxide concentrations range from 255 to 400 μM in LE TPN solutions, while they range from 100 to 175 μM3 6 10 16 in photoprotected preparations. The differences in intermediary metabolism might be associated with differences in peroxides or to other light-induced byproducts generated in the TPN solution 22 23…”