The distribution of 14C-bisphenol A (BPA) in plasma and neuroendocrine organs was determined in Fischer 344 female rats following three oral doses (0.1, 10 or 100mg/kg). Plasma and tissue maximum concentrations (Cmax) were reached within 15-30 min of dosing. Plasma areas-under-the-curve (AUC) ranged from 0.06 to 53.9 microg-h/mL. The AUCs of the pituitary gland and uterus/gonads were 16-21% higher than that of plasma. The AUCs of hypothalamus and the rest of the brain were 43.7% and 77% of the plasma AUCs, respectively. In the brain tissue, the exposure increased linearly with the oral dose, as the dose was increased from 0.1 to 10 and 100 mg/kg; the exposure in the brain relative to the plasma increased by factors of 1, 1.19 and 1.24. This indicates that the brain barrier systems do not limit the access of the lipophilic BPA to the brain. The increases of the uterus/gonads relative to the plasma were 1, 1.07 and 1.04. Tissue partitioning was also examined in vitro by the uptake of 14C-BPA. The BPA tissue/blood partition coefficients were as follows: heart, 7.5; liver, 6.1; kidney, 6.4; fat, 3.6; muscle, 2.6; breast, 3.6; ovaries, 9.1; uterus, 5.9; stomach, 5.1; and small intestine, 6.7. The tissue/cerebrospinal fluid partition coefficients were as follows: pituitary gland, 12.8; brain stem, 6.1; cerebellum, 6.4; hippocampus, 7.1; hypothalamus, 6.1; frontal cortex, 4.9; and caudate nucleus, 6.8.

No abstract

The endotoxin, lipopolysaccharide (LPS), of Salmonella typhimurium was biosynthetically labeled with (3)H and (14)C incorporated into the fatty acyl chains and glucosamine residues, respectively. The radio-labeled LPS was isolated from the bacteria and then injected into Sprague-Dawley rats. The distribution of (14)C and (3)H-LPS in plasma and other organs was determined following intraperitoneal (IP) doses of (14)C and (3)H-LPS (200 μg/kg). Plasma concentrations of both fatty acyl chains and glucosamine residues were biphasic, with a relatively rapid decay followed by a slow decline for 48 h. Similar biphasic results were found in the peripheral organs (kidney and heart) and brain barrier tissues (meninges and choroid plexus). In other brain tissues (brain stem, caudate nucleus, hypothalamus, frontal cortex, cerebellum and hippocampus), the glucosamine residue was biphasic, whereas the fatty acyl chains showed accumulation. Highest concentrations of LPS were found in the plasma, spleen and the liver. In addition, in the liver, sustained elevations of (14)C-glucosamine and (3)H-fatty acyl chains were observed. This indicates LPS accumulation in the liver. By contrast, the spleen showed biphasic decay of glucosamine residues and accumulation of fatty acyl chains. In the brain barrier tissues, peak LPS concentrations were significantly reduced (about 70%) and were further reduced (about 95%) in other brain tissues. The high elevation of LPS in the spleen is considered indicative of an immune response. Our findings highlight the potential significant role of lipid A as shown with the sustained elevation of (3)H-fatty acyl chains in the brain.

No 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.