- Email: [email protected]
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
231±1). Four months later, redox potential, GSH and GSSG Supported by Czech Ministry of Education KONTAKT II grant LH15071.
(nmol/mg prot) were lower in PN groups independently of GSSG addition, relatively to control (respectively, PN
Reference:
groups: -235±1, 69±2, 0.8±0.1 vs. Control: -229±2, 81±5,
1. L. Plecita-Hlavata, et al. Constitutive Reprogramming of
1.8±0.3). ACC activity was higher in PN group (4.5±0.3 U)
Fibroblast
and greater in NP+GSSG groups (5.7±0.3 U) relatively to
Mitochondrial
Metabolism
in
Pulmonary
Hypertension, Am. J. Respir. Cell Mol. Biol. 55 (2016) 47-57
control (3.2±0.2 U). GK and PFK activities did not differ. Conclusion: PN early in life induces later in liver reduction
DOI: 10.1016/j.freeradbiomed.2017.10.276
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.
264
DOI: 10.1016/j.freeradbiomed.2017.10.277
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 Vitor Teixeira1, Thérèse Rouleau1, Guillaume Morin1, Ibrahim Mohamed1, and Jean-Claude Lavoie1 1
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 proGSH. 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 potential
(capillary
electrophoresis,
Dynamic Oxidized Phospholipid Composition within the Liver Plays a Role in Non-alcoholic Fatty Liver Disease Progression
Université de Montréal, Canada
redox
265
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<0.05. Results: Immediately after treatments, there was no difference between groups for redox potential (mV) (-
Clint M Upchurch1, Vlad Serbulea1, and Norbert Leitinger1 1
University of Virginia, USA
Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of cardio-metabolic syndrome, affects up to 25% of individuals within the USA. NAFLD is a progressive pathology initiating with accumulation of fat within the liver
(hepatic
steatosis)
followed
by
inflammation
(steatohepatitis) and liver fibrosis. Currently, drivers of NAFLD progression are poorly understood. Recently, it was shown that fatty acid-induced metabolic dysregulation of hepatocytes results in succinate release. Hepatic stellate cells, the primary instigators of liver fibrosis, have been shown to be activated by succinate, via GPR91, a putative succinate receptor. Here we show that products of phospholipid oxidation increase succinate levels within bone marrow-derived
macrophages.
immunohistochemistry recognizes
oxidized
with
Furthermore,
E06,
phospholipids
an
antibody
(OxPL),
we
using that found
increased E06 staining of carbon tetrachloride treated livers, a model of liver damage, compared to control. To determine the composition of OxPL present within steatotic liver, we developed a liquid chromatography-mass spectrometry method
SfRBM 2017
to
quantify
14
products
of
1-palmitoyl-2-
177
(nmol/mg prot) were lower in PN groups independently of GSSG addition, relatively to control (respectively, PN
Reference:
groups: -235±1, 69±2, 0.8±0.1 vs. Control: -229±2, 81±5,
1. L. Plecita-Hlavata, et al. Constitutive Reprogramming of
1.8±0.3). ACC activity was higher in PN group (4.5±0.3 U)
Fibroblast
and greater in NP+GSSG groups (5.7±0.3 U) relatively to
Mitochondrial
Metabolism
in
Pulmonary
Hypertension, Am. J. Respir. Cell Mol. Biol. 55 (2016) 47-57
control (3.2±0.2 U). GK and PFK activities did not differ. Conclusion: PN early in life induces later in liver reduction
DOI: 10.1016/j.freeradbiomed.2017.10.276
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.
264
DOI: 10.1016/j.freeradbiomed.2017.10.277
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 Vitor Teixeira1, Thérèse Rouleau1, Guillaume Morin1, Ibrahim Mohamed1, and Jean-Claude Lavoie1 1
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 proGSH. 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 potential
(capillary
electrophoresis,
Dynamic Oxidized Phospholipid Composition within the Liver Plays a Role in Non-alcoholic Fatty Liver Disease Progression
Université de Montréal, Canada
redox
265
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<0.05. Results: Immediately after treatments, there was no difference between groups for redox potential (mV) (-
Clint M Upchurch1, Vlad Serbulea1, and Norbert Leitinger1 1
University of Virginia, USA
Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of cardio-metabolic syndrome, affects up to 25% of individuals within the USA. NAFLD is a progressive pathology initiating with accumulation of fat within the liver
(hepatic
steatosis)
followed
by
inflammation
(steatohepatitis) and liver fibrosis. Currently, drivers of NAFLD progression are poorly understood. Recently, it was shown that fatty acid-induced metabolic dysregulation of hepatocytes results in succinate release. Hepatic stellate cells, the primary instigators of liver fibrosis, have been shown to be activated by succinate, via GPR91, a putative succinate receptor. Here we show that products of phospholipid oxidation increase succinate levels within bone marrow-derived
macrophages.
immunohistochemistry recognizes
oxidized
with
Furthermore,
E06,
phospholipids
an
antibody
(OxPL),
we
using that found
increased E06 staining of carbon tetrachloride treated livers, a model of liver damage, compared to control. To determine the composition of OxPL present within steatotic liver, we developed a liquid chromatography-mass spectrometry method
SfRBM 2017
to
quantify
14
products
of
1-palmitoyl-2-
177