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TOXICOLOGY

Interaction between Ascorbate and Light-Exposed Riboflavin Induces Lung Remodeling

Pediatrics Department, Sainte-Justine Hospital, University of Montreal, Montreal, Quebec, Canada (J.C.L., T.R.); and Division of Neonatology, Children's and Women's Health Centre of British Columbia, Vancouver, British Columbia, Canada (P.C.)

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), -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 (r² = 0.35; p < 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.

Address correspondence to: Dr. Jean-Claude Lavoie, Research Centre, Sainte-Justine Hospital, 3175 Côte Ste-Catherine, Montreal, QC, Canada H3T 1C5. E-mail: jclavoie{at}justine.umontreal.ca