title: Free fatty acids profile of the fetal brain and the plasma, liver, brain and kidneys of pregnant rats treated with sodium arsenite at mid-organogenesis.
abstract: Free fatty acids (FFAs) are known to be markers of cellular membrane degradation through lipid peroxidation and are substrates for the production of reactive oxygen species (ROS). Oxidative stress, due to overproduction of ROS, may facilitate cellular insult by various toxicants. The ability of the rat conceptus to respond to toxic stress may be critical for normal development. In this study, the effects of the environmental toxicant sodium arsenite (NaAsO₂) on FFAs were investigated after administering a single oral dose, in water and in a lipid medium, to pregnant rats on gestational day (GD) 10, a time point at mid-organogenesis. NaAsO₂ was administered in deionized water (AsH₂O) or in half and half dairy cream (AsHH) at a dose of 41 mg sodium arsenite (NaAsO₂)/kg body weight. Control animals were treated with either dairy cream (HH) or deionized water (H₂O). The animals were sacrificed on GD 20. The fetal brain and the maternal liver, brain, plasma and kidneys were harvested. The FFAs were extracted and analyzed by gas chromatography. In the liver, there was an increase of myristic acid (1200%), myristoleic acid (174%), palmitic acid (47%), elaidic acid (456%), oleic acid (165%) and docosahexaenoic acid (224%) in the AsH₂O group as compared to the AsHH group. Oleic acid and arachidonic acid were increased by 192% and 900%, respectively, in the AsH₂O group as compared to the H₂O group, and myristic acid was decreased by 90% in the AsHH group as compared to the HH group. In the maternal brain, myristoleic acid was decreased by 91% in the AsH₂O group as compared to the H₂O group, and DHA increased by 148% in the AsHH group as compared to the HH group. In the fetal brain, myristic and stearic acids were decreased by 87% and 89%, respectively, in the AsH₂O group as compared to the AsHH group. Myristic, stearic and arachidonic acids were increased by 411%, 265%, and 144%, respectively, in the AsHH group as compared to the HH group. There was no effect on the fatty acids concentrations in the kidney or plasma as compared to controls. This study shows that NaAsO₂ produced a differential effect on the fatty acid profiles in rats. Further investigation is needed to elucidate the role of fatty acids in differential signaling and regulation by either the palmitoylation or myristoylation process of cellular functions in these target organs.
authors.affiliation: Center for Food Safety and Applied Nutrition, Division of Toxicology, Office of Applied Research and Safety Assessment, Laurel, MD, USA. rossivan@msn.com
authors.forename: Ivan A
authors.initials: IA
authors.lastname: Ross
authors.forename: Thomas
authors.initials: T
authors.lastname: Boyle
authors.forename: Widmark D
authors.initials: WD
authors.lastname: Johnson
authors.forename: Robert L
authors.initials: RL
authors.lastname: Sprando
authors.forename: Michael W
authors.initials: MW
authors.lastname: O'Donnell
authors.forename: Dennis
authors.initials: D
authors.lastname: Ruggles
authors.forename: Chung S
authors.initials: CS
authors.lastname: Kim
mesh_terms: D000818:Animals; D018053:Arsenites / Q000633:toxicity*; D001921:Brain / Q000196:embryology / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000196:embryology / Q000378:metabolism*; D007668:Kidney / Q000196:embryology / Q000378:metabolism; D008099:Liver / Q000196:embryology / Q000378:metabolism; D038081:Organogenesis / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017670:Sodium Compounds / Q000633:toxicity*
chemical_list: D018053:Arsenites; D004785:Environmental Pollutants; D005227:Fatty Acids; D017670:Sodium Compounds; C017947:sodium arsenite