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

被引:33
作者
Knafo, L
Chessex, P
Rouleau, T
Lavoie, JC
机构
[1] Univ Montreal, Res Ctr, CHU St Justine, Montreal, PQ H3T 1C5, Canada
[2] Univ Montreal, Dept Paediat, CHU St Justine, Montreal, PQ H3T 1C5, Canada
[3] Childrens & Womens Hlth Ctr British Columbia, Div Neonatol, Vancouver, BC, Canada
关键词
D O I
10.1373/clinchem.2005.050427
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 [基础医学];
摘要
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 (alpha = 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 have peroxide and aldehyde functions. 2005 American Association for Clinical Chemistry.
引用
收藏
页码:1462 / 1471
页数:10
相关论文
共 37 条
[1]
ALLRED B, 1983, J LIPID RES, V24, P449
[2]
BATHIA J, 1982, J PEDIAT, V96, P284
[3]
TOTAL PARENTERAL NUTRITION-ASSOCIATED CHOLESTASIS IN RATS - COMPARISON OF DIFFERENT AMINO-ACID MIXTURES [J].
BELLI, DC ;
FOURNIER, LA ;
LEPAGE, G ;
YOUSEF, I ;
WEBER, AM ;
TUCHWEBER, B ;
ROY, CC .
JOURNAL OF PARENTERAL AND ENTERAL NUTRITION, 1987, 11 (01) :67-73
[4]
Bimodal activation of acetyl-CoA carboxylase by glutamate [J].
Boone, AN ;
Chan, A ;
Kulpa, JE ;
Brownsey, RW .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (15) :10819-10825
[5]
Effect of sodium metabisulfite on hydrogen peroxide production in light-exposed pediatric parenteral amino acid solutions [J].
Brawley, V ;
Bhatia, J ;
Karp, WB .
AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY, 1998, 55 (12) :1288-1292
[6]
Survival of guinea pig pups in hyperoxia is improved by enhanced nutritional substrate availability for glutathione production [J].
Chessex, P ;
Lavoie, JC ;
Laborie, S ;
Vallée, J .
PEDIATRIC RESEARCH, 1999, 46 (03) :305-310
[7]
Chessex P, 2002, PEDIATR RES, V52, P958, DOI [10.1203/01.PDR.0000034236.69144.AC, 10.1203/00006450-200212000-00023]
[8]
Parenteral multivitamin supplementation induces both oxidant and antioxidant responses in the liver of newborn guinea pigs [J].
Chessex, P ;
Lavoie, JC ;
Laborie, S ;
Rouleau, T .
JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION, 2001, 32 (03) :316-321
[9]
Photoprotection of solutions of parenteral nutrition decreases the infused load as well as the urinary excretion of peroxides in premature infants [J].
Chessex, P ;
Laborie, S ;
Lavoie, JC ;
Rouleau, T .
SEMINARS IN PERINATOLOGY, 2001, 25 (02) :55-59
[10]
An electrospray ionization ion trap mass spectrometric (ESI-MS-MSn) study of dehydroascorbic acid hydrolysis at neutral pH [J].
Cioffi, N ;
Losito, I ;
Terzano, R ;
Zambonin, CG .
ANALYST, 2000, 125 (12) :2244-2248