Received on March 2, 2005
Accepted on May 12, 2005

Drug Monitoring and Toxicology

Association between Hydrogen Peroxide-Dependent Byproducts of Ascorbic Acid and Increased Hepatic Acetyl-CoA Carboxylase Activity

¹ Research Centre and Paediatric Department, CHU Sainte-Justine, University of Montreal, Montreal, Quebec, Canada
² Division of Neonatology, Children's and Women's Health Centre of British Columbia, Vancouver, British Columbia, Canada

^* To whom correspondence should be addressed. E-mail: jean-claude.lavoie{at}umontreal.ca.

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 H₂O₂ and molecules with masses of 136 and 208. We hypothesized that H₂O₂ initiates the peroxidation of ascorbic acid (AA), producing biologically active byproducts affecting hepatic lipid metabolism.

Methods: Mass spectrometry (MS) documented the participation of H₂O₂ 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 · kg^-1 · day^-1, enriched with control or test mixtures, for 4 days. The control mixture was photo-protected AA + Ribo (without byproducts or H₂O₂), and the test mixture was AA + Ribo treated to generate AA byproducts without H₂O₂. Hepatic acetyl-CoA carboxylase (ACC) activity was determined after 4 days. Fourth-day urine samples were analyzed by MS. Data were treated by ANOVA ( = 0.05).

Results: H₂O₂ 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 H₂O₂ 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: H₂O₂ 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 may have peroxide and aldehyde functions.