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Clin Chem. 2005 Aug;51(8):1462-71. Epub 2005 Jun 10.

Association between hydrogen peroxide-dependent byproducts of ascorbic acid and increased hepatic acetyl-CoA carboxylase activity.

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1
Research Centre and Paediatric Department, CHU Sainte-Justine, University of Montreal, Montreal, Quebec, Canada.

Abstract

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.

PMID:
15951314
DOI:
10.1373/clinchem.2005.050427
[Indexed for MEDLINE]
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