Association between hydrogen peroxide-dependent byproducts of ascorbic acid and increased hepatic acetyl-CoA carboxylase activity.
BACKGROUND
Parenteral multivitamin preparation (MVP) induces fatty liver in neonatal guinea pig pups; this is prevented by photoprotection. Photo-excited riboflavin present in MVP generates H(2)O(2) and molecules with masses of 136 and 208. We hypothesized that H(2)O(2) initiates the peroxidation of ascorbic acid (AA), producing biologically active byproducts affecting hepatic lipid metabolism.


METHODS
Mass spectrometry (MS) documented the participation of H(2)O(2) and photo-excited riboflavin (Ribo) in the formation of AA byproducts. Sixteen 3-day-old guinea pig pups received an intravenous solution (50 g/L dextrose + 4.5 g/L NaCl + 1 kIU/L heparin) at 240 mL x kg(-1) x day(-1), enriched with control or test mixtures, for 4 days. The control mixture was photo-protected AA + Ribo (without byproducts or H(2)O(2)), and the test mixture was AA + Ribo treated to generate AA byproducts without H(2)O(2). Hepatic acetyl-CoA carboxylase (ACC) activity was determined after 4 days. Fourth-day urine samples were analyzed by MS. Data were treated by ANOVA (alpha = 0.05).


RESULTS
H(2)O(2) did not influence the classic degradation of AA, as the generation of 2,3-diketogulonic acid was not affected. In contrast, the formation of molecules with masses of 136 and 208 was H(2)O(2) and time dependent. ACC activity was higher (P <0.01) in animals receiving high concentration of these molecules; its hepatic activation correlated (P <0.01) with the urinary concentration of molecule-208.


CONCLUSIONS
H(2)O(2) at concentrations found in the clinical setting of total parenteral nutrition induce the transformation of dehydroascorbic acid into compounds that have the potential to affect lipid metabolism. These molecules have peroxide and aldehyde functions.
Knafo
Laurent
L
Research Centre and Paediatric Department, CHU Sainte-Justine, University of Montreal, Montreal, Quebec, Canada.
Chessex
Philippe
P
Rouleau
Thérèse
T
Lavoie
Jean-Claude
JC
D000103:Acetyl-CoA Carboxylase / Q000378:metabolism*; D000818:Animals; D001205:Ascorbic Acid / Q000737:chemistry / Q000378:metabolism*; D002087:Butyrates / Q000737:chemistry; D006168:Guinea Pigs; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000378:metabolism*; D008027:Light; D050356:Lipid Metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D013058:Mass Spectrometry; D015394:Molecular Structure; D008970:Molecular Weight; D010084:Oxidation-Reduction; D012256:Riboflavin / Q000737:chemistry / Q000378:metabolism / Q000528:radiation effects
D002087:Butyrates; D006861:Hydrogen Peroxide; D000103:Acetyl-CoA Carboxylase; C011369:threonic acid; D001205:Ascorbic Acid; D012256:Riboflavin