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, H(2)O(2)+/- 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.
Lavoie
Jean-Claude
JC
Research Centre, Sainte-Justine Hospital, 3175 Côte Ste-Catherine, Montreal, Quebec, Canada H3T 1C5. jclavoie@justine.umontreal.ca
Rouleau
Thérèse
T
Chessex
Philippe
P
D000818:Animals; D001205:Ascorbic Acid / Q000009:adverse effects*; D004195:Disease Models, Animal; D004347:Drug Interactions; D006168:Guinea Pigs; D008027:Light; D008171:Lung Diseases / Q000139:chemically induced*; D012256:Riboflavin / Q000009:adverse effects* / Q000528:radiation effects
D001205:Ascorbic Acid; D012256:Riboflavin