Long-term Impact of added Glutathione into Parenteral Nutrition Administered During the First week of life on Redox Potential and Energy Metabolism Enzymes in Guinea pig liver

Abstract

Introduction Peroxides are generated in parenteral nutrition (PN). Infusion of PN or H2O2 in the first week of life of animals alters later in life their hepatic energy metabolism. Glutathione addition in PN prevented pulmonary oxidative stress induced by PN in newborn guinea pigs (GP). Hypothesis: Addition of glutathione into PN prevents the long-term impact of PN on activities of key enzymes of energy metabolism (glucokinase (GK), phosphofructokinase (PFK) and acetyl-CoA carboxylase (ACC)). Methods 4 groups (N=48) of 3-day old GP were used. Control: no manipulation, fed ad libitum all time; PN: animals nourished exclusively with a complete PN via a catheter; PN+ 6 or 12 µM GSSG; GSSG was used as pro-GSH. After 4 days, hepatic redox potential was measured in half of GP. The other half started oral diet. At 16 weeks of age, liver was collected for determination of GSH, GSSG and redox potential (capillary electrophoresis, Nernst’s equation), activities (U: nmol/min/mg prot) of PFK, GK (calorimetric method), and ACC (method with radioactive tracer). Data (mean±sem) were analyzed by ANOVA, p Results Immediately after treatments, there was no difference between groups for redox potential (mV) (-231±1). Four months later, redox potential, GSH and GSSG (nmol/mg prot) were lower in PN groups independently of GSSG addition, relatively to control (respectively, PN groups: -235±1, 69±2, 0.8±0.1 vs. Control: -229±2, 81±5, 1.8±0.3). ACC activity was higher in PN group (4.5±0.3 U) and greater in NP+GSSG groups (5.7±0.3 U) relatively to control (3.2±0.2 U). GK and PFK activities did not differ. Conclusion PN early in life induces later in liver reduction of redox potential and higher activity of a key enzyme of lipogenesis (ACC). In contrast to beneficial effect previously observed in lungs, addition of GSSG into PN did not prevent the long-term effects of PN on the liver.