title: Comparative toxicity of oleic and linoleic acid on human lymphocytes.
abstract: Commercially available lipid emulsions for parenteral nutrition are mainly composed by long chain triacylglycerol containing a high proportion of linoleic acid (LA) or oleic acid (OA). The immunological impact of such therapy is particularly important because parenteral diets are often administered to critically ill patients as a mechanism to supply adequate nutrition during catabolic stress conditions. The comparative toxicity of OA and LA on human lymphocytes and the type of cell death induced by these fatty acids were determined in vitro. Parameters of cell death were investigated by flow cytometry-cell viability, DNA fragmentation, phosphatidylserine externalization, mitochondrial depolarization, neutral lipid accumulation and production of reactive oxygen species-and by fluorescence microscopy-chromatin condensation. Additionally a spectrofluorometric assay was employed to determine the activities of caspase--3, 6 and 8. Evidence is presented herein that OA is less toxic to human lymphocytes than LA. However, both fatty acids promoted apoptosis and necrosis of these cells. The mechanism of cell death induced by OA involved activation of caspase 3 while the mechanism of death induced by LA involved mitochondrial depolarization and ROS production. Importantly, neutral lipid accumulation may be a mechanism to protect lymphocytes against the toxicity induced by OA. OA may offer an immunological less problematic alternative to LA with respect to fatty acid composition of parenteral nutritional emulsions.
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, Av. Prof. Lineu Prestes, 1524, CEP 05508-900, University of São Paulo, SP, Brazil. mafecury@icb.usp.br
authors.forename: Maria F
authors.initials: MF
authors.lastname: Cury-Boaventura
authors.forename: Renata
authors.initials: R
authors.lastname: Gorjão
authors.forename: Thaís Martins
authors.initials: TM
authors.lastname: de Lima
authors.forename: Philip
authors.initials: P
authors.lastname: Newsholme
authors.forename: Rui
authors.initials: R
authors.lastname: Curi
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D019787:Linoleic Acid / Q000633:toxicity*; D008214:Lymphocytes / Q000187:drug effects / Q000473:pathology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000502:physiology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D019301:Oleic Acid / Q000633:toxicity*; D010718:Phosphatidylserines / Q000097:blood; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D010718:Phosphatidylserines; D017382:Reactive Oxygen Species; D019301:Oleic Acid; D019787:Linoleic Acid