RT Journal Article
SR Electronic
T1 Ascorbylperoxide Contaminating Parenteral Nutrition Perturbs the Lipid Metabolism in Newborn Guinea Pig
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 278
OP 284
DO 10.1124/jpet.110.166223
VO 334
IS 1
A1 Raffi Maghdessian
A1 François Côté
A1 Thérèse Rouleau
A1 Ali Ben Djoudi Ouadda
A1 Émile Levy
A1 Jean-Claude Lavoie
YR 2010
UL http://jpet.aspetjournals.org/content/334/1/278.abstract
AB The light exposure of parenteral nutritive solutions generates peroxides such as H2O2 and ascorbylperoxide [2,3-diketo-4-hydoxyperoxyl-5,6-dihydroxyhexanoic acid]. This absence of photoprotection is associated with higher plasma triacylglycerol (TG) concentration in premature infants and oxidative stress and H2O2-independent hepatic steatosis in animals. We hypothesized that ascorbylperoxide is the active agent leading to high TG. The aim was to investigate the role of ascorbylperoxide in glucose and lipid metabolism in an animal model of neonatal parenteral nutrition. Three-day-old guinea pigs received through a catheter in the jugular solutions containing dextrose plus 0, 90, 225, or 450 μM ascorbylperoxide. After 4 days, blood and liver were sampled and treated for determinations of TG, cholesterol, markers of oxidative stress (redox potential of glutathione and F2α-isoprostane), and activities and protein levels of acetyl-CoA carboxylase (ACC), glucokinase, and phosphofructokinase (PFK). Ascorbylperoxide concentration was measured in urine on the last day. Data were compared by analysis of variance (p < 0.05). Plasma TG and cholesterol and hepatic PFK activity increased (200% of control), whereas ACC activity decreased (66% of control) in the function of the amount of ascorbylperoxide infused. Both markers of oxidative stress were higher in animals receiving the highest amounts of ascorbylperoxide. The logarithmic relations between urinary ascorbylperoxide and plasma TG (r2 = 0.69) and hepatic PFK activity (r2 = 0.26) were positive, whereas they were negative with ACC activity (r2 = 0.50). In conclusion, ascorbylperoxide contaminating parenteral nutrition stimulates glycolysis, allowing higher availability of substrates for lipid synthesis. The logarithmic relation between urinary ascorbylperoxide and plasma TG suggests a very low efficient concentration. Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics