scholarly journals Glutathione Supplementation of Parenteral Nutrition Prevents Oxidative Stress and Sustains Protein Synthesis in Guinea Pig Model

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2063 ◽  
Author(s):  
Guillaume Morin ◽  
Clémence Guiraut ◽  
Marisol Perez Marcogliese ◽  
Ibrahim Mohamed ◽  
Jean-Claude Lavoie

Peroxides contaminating parenteral nutrition (PN) limit the use of methionine as a precursor of cysteine. Thus, PN causes a cysteine deficiency, characterized by low levels of glutathione, the main molecule used in peroxide detoxification, and limited growth in individuals receiving long-term PN compared to the average population. We hypothesize that glutathione supplementation in PN can be used as a pro-cysteine that improves glutathione levels and protein synthesis and reduces oxidative stress caused by PN. One-month-old guinea pigs (7–8 per group) were used to compare glutathione-enriched to a non-enriched PN, animals on enteral nutrition were used as a reference. PN: Dextrose, amino acids (Primene), lipid emulsion (Intralipid), multivitamins, electrolytes; five-day infusion. Glutathione (GSH, GSSG, redox potential) and the incorporation of radioactive leucine into the protein fraction (protein synthesis index) were measured in the blood, lungs, liver, and gastrocnemius muscle. Data were analysed by ANOVA; p < 0.05 was considered significant. The addition of glutathione to PN prevented the PN-induced oxidative stress in the lungs and muscles and supported protein synthesis in liver and muscles. The results potentially support the recommendation to add glutathione to the PN and demonstrate that glutathione could act as a biologically available cysteine precursor.

2021 ◽  
Vol 8 ◽  
Author(s):  
Pegah Bagheri ◽  
Khang Hoang ◽  
Anthony A. Fung ◽  
Sahran Hussain ◽  
Lingyan Shi

Oxidative imbalance plays an essential role in the progression of many diseases that include cancer and neurodegenerative diseases. Aromatic amino acids (AAA) such as phenylalanine and tryptophan have the capability of escalating oxidative stress because of their involvement in the production of Reactive Oxygen Species (ROS). Here, we use D2O (heavy water) probed stimulated Raman scattering microscopy (DO-SRS) and two Photon Excitation Fluorescence (2PEF) microscopy as a multimodal imaging approach to visualize metabolic changes in HeLa cells under excess AAA such as phenylalanine or trytophan in culture media. The cellular spatial distribution of de novo lipogenesis, new protein synthesis, NADH, Flavin, unsaturated lipids, and saturated lipids were all imaged and quantified in this experiment. Our studies reveal ∼10% increase in de novo lipogenesis and the ratio of NADH to flavin, and ∼50% increase of the ratio of unsaturated lipids to saturated lipid in cells treated with excess phenylalanine or trytophan. In contrast, these cells exhibited a decrease in the protein synthesis rate by ∼10% under these AAA treatments. The cellular metabolic activities of these biomolecules are indicators of elevated oxidative stress and mitochondrial dysfunction. Furthermore, 3D reconstruction images of lipid droplets were acquired and quantified to observe their spatial distribution around cells’ nuceli under different AAA culture media. We observed a higher number of lipid droplets in excess AAA conditions. Our study showcases that DO-SRS imaging can be used to quantitatively study how excess AAA regulates metabolic activities of cells with subcellular resolution in situ.


Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2495
Author(s):  
Mikołaj Danko ◽  
Aleksandra Żyła-Pawlak ◽  
Janusz Książyk ◽  
Katarzyna Olszewska-Durkacz ◽  
Marta Sibilska ◽  
...  

Background: Deterioration of liver function, or intestinal failure-associated liver disease, is often observed in long-term parenterally fed children. Fish oil-based intravenous lipids have been reported to play a role in the prevention and treatment of intestinal failure associated liver disease. Methods: This retrospective analysis included 40 pediatric patients, (20 male and 20 female), median age 38 months (range 1.5–200 months) on long-term (≥1 month) parenteral nutrition who received the parenteral mixtures containing a combination of a third-generation lipid emulsion and pure fish oil because of laboratory liver function abnormalities. The total dose of fish oil from both emulsions for each patient exceeded 0.5 g/kg/day. Data from visits in an outpatient clinic were retrospectively analyzed using the Wilcoxon test, Mann-Whitney test, and Spearman correlation test. Results: The median time of therapy was 149 days (range 28–418 days). There was a decrease of median total and direct (conjugated) bilirubin concentration from 22.23 µmol/L (range 3.42–243 µmol/L) to 10.26 µmol/L (range 3.42–180.58 µmol/L; p < 0.005) and 8.55 (range 1.71–212.04 µmol/L) to 6.84 µmol/L (range 1.71–150.48 µmol/L; p < 0.007) respectively. A significant decrease in median alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase was also observed. In 11 patients bilirubin concentrations increased or remained unchanged. When compared to the patients who responded to the combination therapy, the patients who did not respond received parenteral nutrition for a longer time prior to the start of the therapy (51 vs. 30 months; p < 0.05). Conclusions: The mixture of an intravenous lipid emulsion containing soybean oil, medium-chain triglycerides, olive oil, and fish oil with the addition of pure fish oil emulsion may be helpful in the treatment of liver complications in children on long-term parenteral nutrition.


2015 ◽  
Vol 20 (3) ◽  
pp. 217-221
Author(s):  
Ting Ting Wu ◽  
David S. Hoff

A syndrome of hepatosplenomegaly, thrombocytopenia, and anemia and the presence of sea-blue histiocytes in bone marrow has been associated with parenteral soybean oil administration in patients receiving long-term total parenteral nutrition (TPN). A case is described here where this syndrome was observed in a pediatric patient who received long-term parenteral fish oil nutrition.


2006 ◽  
Vol 291 (1) ◽  
pp. E159-E166 ◽  
Author(s):  
Renan A. Orellana ◽  
Pamela M. J. O'Connor ◽  
Jill A. Bush ◽  
Agus Suryawan ◽  
M. Carole Thivierge ◽  
...  

Sepsis promotes insulin resistance and reduces protein synthesis in skeletal muscle of adults. The effect of sepsis on insulin-stimulated muscle protein synthesis has not been determined in neonates, a highly anabolic population that is uniquely sensitive to insulin. Overnight fasted neonatal pigs were infused for 8 h with endotoxin [lipopolysaccharide (LPS), 0 and 10 μg·kg−1·h−1]. Glucose and amino acids were maintained at fasting levels, insulin was clamped at either fasting or fed (2 or 10 μU/ml) levels, and fractional protein synthesis rates were determined at the end of the infusion. LPS infusion induced a septic-like state, as indicated by a sustained elevation in body temperature, heart rate, and cortisol. At fasting insulin levels, LPS reduced fractional protein synthesis rates in gastrocnemius muscle (−26%) but had no effect on the masseter and heart. By contrast, LPS stimulated liver protein synthesis (+28%). Increasing insulin to fed levels accelerated protein synthesis rates in gastrocnemius (controls by +38%, LPS by +60%), masseter (controls by +50%, LPS by +43%), heart (controls by +34%, LPS by +40%), and diaphragm (controls by +54%, LPS by +29%), and the response to insulin was similar in LPS and controls. Insulin did not alter protein synthesis in liver, kidney, or jejunum in either group. These findings suggest that acute endotoxemia lowers basal fasting muscle protein synthesis in neonates but does not alter the response of protein synthesis to insulin.


Author(s):  
Feng Xiong ◽  
Qin Li ◽  
Bo Zhou ◽  
Jiongli Huang ◽  
Guiqiang Liang ◽  
...  

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