Blood Clearance and Tissue Uptake of Intravenous Lipid Emulsions Containing Long-Chain and Medium-Chain Triglycerides and Fish Oil in a Mouse Model

1999 ◽  
Vol 23 (5) ◽  
pp. 253-259 ◽  
Author(s):  
Erena Treskova ◽  
Yvon A. Carpentier ◽  
Rajasekhar Ramakrishnan ◽  
Maysoon Al-Haideri ◽  
Toru Seo ◽  
...  
2006 ◽  
Vol 136 (11) ◽  
pp. 2766-2772 ◽  
Author(s):  
Kemin Qi ◽  
Toru Seo ◽  
Zaifang Jiang ◽  
Yvon A. Carpentier ◽  
Richard J. Deckelbaum

Gut ◽  
1999 ◽  
Vol 45 (3) ◽  
pp. 453-458 ◽  
Author(s):  
R Pakula ◽  
F M Konikoff ◽  
A M Moser ◽  
F Greif ◽  
A Tietz ◽  
...  

BACKGROUNDPatients on parenteral nutrition have an increased incidence of gall bladder sludge and gallstone disease, thought to be related to bile stasis. Intravenous lipid emulsions, especially those containing medium chain triglycerides, have also been shown to have a lithogenic effect on the composition of bile in the gall bladder.AIMSTo determine whether lipid infusion influences hepatic bile composition in patients with an indwelling T tube following cholecystectomy and choledochotomy.METHODSIn eight patients undergoing the above surgical procedure, the time at which effects of the interrupted enterohepatic circulation were minimal was determined. Twenty two cholesterol gallstone patients with bile fistula were then randomised to receive an infusion of a lipid emulsion containing either long chain triglycerides or a mixture of long and medium chain triglycerides.RESULTSLipid infusion resulted in a significant increase in plasma levels of triglycerides and phospholipids. Both lipid emulsions caused an increase in hepatic biliary cholesterol level and cholesterol saturation index, but this effect was more pronounced with medium chain triglycerides. The fatty acid composition of biliary phospholipids showed a significant enrichment of linoleic acid by both lipid infusions.CONCLUSIONSInfusion of triglycerides causes lithogenic changes in hepatic bile composition in humans, the lithogenic effect of infusion of medium chain triglycerides being more pronounced than that of long chain triglycerides. This effect, coupled with gall bladder stasis, may be responsible for the increased risk of biliary sludge and gallstone formation in patients on long term lipid infusion.


2019 ◽  
Vol 109 (4) ◽  
pp. 1038-1050 ◽  
Author(s):  
Meredith A Baker ◽  
Bennet S Cho ◽  
Lorenzo Anez-Bustillos ◽  
Duy T Dao ◽  
Amy Pan ◽  
...  

ABSTRACT Background Fish oil (FO) intravenous lipid emulsions (ILEs) are used as a monotherapy to treat parenteral nutrition (PN)-associated liver disease and provide essential fatty acids (EFAs) needed to sustain growth and prevent EFA deficiency (EFAD). Studies have suggested that medium-chain triglycerides (MCTs) and α-tocopherol have anti-inflammatory properties. Objective The purpose of this study was to test whether FO-ILEs containing MCTs and/or additional α-tocopherol decrease the inflammatory response to an endotoxin challenge compared with FO-ILE alone and preserve the ability to prevent PN-induced liver injury in mice. Methods A murine model of PN-induced hepatosteatosis was used to compare the effects of ILEs formulated in the laboratory containing varying ratios of FO and MCTs, and subsequently FO- and 50:50 FO:MCT-ILE plus 500 mg/L α-tocopherol (FO + AT and 50:50 + AT, respectively). C57BL/6 mice receiving unpurified diet (UPD), PN-equivalent diet (PN) + saline, and PN + soybean oil (SO)-ILE served as controls. After 19 d, mice received an intraperitoneal saline or endotoxin challenge 4 h before being killed. Serum and livers were harvested for histologic analysis, fatty acid profiling, and measurement of systemic inflammatory markers (tumor necrosis factor-α, interleukin-6). Results All ILEs were well tolerated and prevented biochemical EFAD. Livers of mice that received saline and SO developed steatosis. Mice that received 30:70 FO:MCT developed mild hepatosteatosis. All other FO-containing ILEs preserved normal hepatic architecture. Mice that received FO- or SO-ILE had significantly elevated systemic inflammatory markers after endotoxin challenge compared with UPD-fed controls, whereas 50:50 FO:MCT, 30:70 FO:MCT, FO + AT, and 50:50 + AT groups had significantly lower inflammatory markers similar to those seen in UPD-fed controls. Conclusions Mixed FO/MCT and the addition of α-tocopherol to FO improved the inflammatory response to endotoxin challenge compared with FO-ILE alone while still preventing PN-induced liver injury and EFAD in mice. There was no synergistic relation between α-tocopherol and MCTs.


Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 508
Author(s):  
Gregory Guthrie ◽  
Douglas Burrin

Total parenteral nutrition (TPN) is a life-saving intervention for infants that are unable to feed by mouth. Infants that remain on TPN for extended periods of time are at risk for the development of liver injury in the form of parenteral nutrition associated cholestasis (PNAC). Current research suggests the lipid component of TPN is a factor in the development of PNAC. Most notably, the fatty acid composition, vitamin E concentration, and presence of phytosterols are believed key mediators of lipid emulsion driven PNAC development. New emulsions comprised of fish oil and medium chain triglycerides show promise for reducing the incidence of PNAC in infants. In this review we will cover the current clinical studies on the benefit of fish oil and medium chain triglyceride containing lipid emulsions on the development of PNAC, the current constituents of lipid emulsions that may modulate the prevalence of PNAC, and potential new supplements to TPN to further reduce the incidence of PNAC.


2009 ◽  
Vol 110 (2) ◽  
pp. 380-386 ◽  
Author(s):  
Jean-Xavier Mazoit ◽  
Régine Le Guen ◽  
Hélène Beloeil ◽  
Dan Benhamou

Background Rapid infusion of lipid emulsion has been proposed to treat local anesthetic toxicity. The authors wanted to test the buffering properties of two commercially available emulsions made of long- and of long- and medium-chain triglycerides. Methods Using the shake-flask method, the authors measured the solubility and binding of racemic bupivacaine, levobupivacaine, and ropivacaine to diluted Intralipid (Fresenius Kabi, Paris, France) and Medialipide (B-Braun, Boulogne, France). Results The apparent distribution coefficient expressed as the ratio of mole fraction was 823 +/- 198 and 320 +/- 65 for racemic bupivacaine and levobupivacaine, and ropivacaine, respectively, at 500 mg in the Medialipide/buffer emulsion; and 1,870 +/- 92 and 1,240 +/- 14 for racemic bupivacaine and levobupivacaine, and ropivacaine, respectively, in the Intralipid/buffer emulsion. Decreasing the pH from 7.40 to 7.00 of the Medialipide/buffer emulsion led to a decrease in ratio of molar concentration from 121 +/- 3.8 to 46 +/- 2.8 for bupivacaine, and to a lesser extent from 51 +/- 4.0 to 31 +/- 1.6 for ropivacaine. The capacity of the 1% emulsions was 871 and 2,200 microM for the 1% Medialipide and Intralipid emulsions, respectively. The dissociation constant was 818 and 2,120 microM for racemic bupivacaine and levobupivacaine, and ropivacaine, respectively. Increasing the temperature from 20 to 37 degrees C led to a greater increase in affinity for ropivacaine (55%) than for bupivacaine (27%). When the pH of the buffer was decreased from 7.40 to 7.00, the affinity was decreased by a factor of 1.68, similar for both anesthetics. Conclusions The solubility of long-acting local anesthetics in lipid emulsions and the high capacity of binding of these emulsions most probably explain their clinical efficacy in case of toxicity. The long-chain triglyceride emulsion Intralipid appears to be about 2.5 times more efficacious than the 50/50 medium-chain/long-chain Medialipide emulsion. Also, because of their higher hydrophobicity, racemic bupivacaine and levobupivacaine seem to clear more rapidly than ropivacaine.


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