Whitfield, Phillip David; (1998) Analysis of intravenous lipid emulsions and their effect on cellular structure and function. Doctoral thesis (Ph.D.), University College London (United Kingdom).

Text Analysis_of_intravenous_lipid_.pdf Download (10MB)

Abstract

Total parenteral nutrition (TPN) offers the chance of survival to children who have had extensive gut resections or suffer from severe gut failure. However, in infants it is often associated with serious complications including cholestatic liver disease. The aetiology of these complications remains unclear ahhough it has been suggested that the lipid emulsions used in TPN may be responsible. Commercial fat emulsions are typically made up of a complex mixture of soybean oil-derived long chain triglycerides emulsified with natural phospholipids and contain significant quantities of sterol contaminants in the form of plant sterols and cholesterol. The hypothesis underlying this study was that components of the lipid emulsions, in particular plant sterols and/or phospholipids, may play a role in the development of TPN-associated cholestasis. The following methods were established and validated during the course of this project i) the measurement of membrane fluidity of erythrocyte ghosts by fluorescence polarography, ii) the quantification of lipids from both cells in tissue culture and patient samples using gas chromatography-mass spectrometry, iii) an in vitro system to study the effect of lipid emulsions and their component fractions on cholesterol uptake and efflux using cultured Hep G2 cells and iv) the characterisation of the structure of phospholipids in lipid emulsions by electrospray ionisation-tandem mass spectrometry. Results showed a) the accumulation of phytosterols in plasma and erythrocyte membranes of patients receiving TPN and a positive correlation between erythrocyte membrane lipid composition and membrane fluidity, b) the TPN lipid emulsions had a dose-dependent inhibitory effect on cholesterol uptake by Hep G2 cells, c) the phospholipid-rich particles of the lipid emulsion which also contain high concentrations of phytosterols were primarily responsible for producing the effects noted above and d) electrospray ionisation-tandem mass spectrometry could be used to make comparisons of the polar head group, acyl substituents and the positional placement of the fatty acid side chains of the phospholipids found in the lipid emulsions frequently used in TPN regimes. In conclusion, these results indicated that a component or components of the lipid emulsions may interfere with cellular lipid homeostasis in vivo and may thus play a role in the development of TPN-associated cholestasis. Further work is required to differentiate between the effects caused by plant sterols and phospholipids.

Download activity - last month

Export as XMLCSVJSON

Download activity - last 12 months

Export as CSVJSONXML

Downloads by country - last 12 months

Export as XMLCSVJSON

Archive Staff Only

View Item