oleoylanilide and Body-Weight

Toxic oil syndrome (TOS) is caused by ingestion of denatured edible oils. Even though the etiology and pathogenesis of this disease are not fully known, it is quite clear that generation of free radicals caused by ingestion of fatty acid anilides is responsible for the pathogenetic mechanism in many TOS patients. Fatty acid anilides may also alter the free radical status of lungs and erythrocytes; this possibility may shed some light on understanding toxic oil syndrome. The present study describes the effects of oral administration of fatty acid anilides on the activities of major enzymes involved in the oxygen defense systems of lungs and erythrocytes. Feeding fatty acid anilides caused an increase in the superoxide dismutase (SOD) activity in erythrocytes, whereas it caused a decrease in the SOD activity in lungs. GSH-Px activity was not significantly changed in erythrocytes but was decreased in lungs. Although the activity of catalase was increased only by a higher dose in the erythrocytes, it was not affected in the lung at any dosage. Even though the ingestion of fatty acid anilides caused an increase in the SOD activity in the erythrocytes and a decrease in the SOD activity in the lungs, there was an increase in the lipid peroxidation in both cases. The increase in lipid peroxidation in erythrocytes is probably caused by the accumulation of H2O2, and that in the lungs is due to the accumulation of superoxide anion.

Topics: Anilides; Animals; Body Weight; Brassica; Catalase; Erythrocytes; Fatty Acids, Monounsaturated; Free Radicals; Glutathione Peroxidase; Guinea Pigs; Linoleic Acids; Lipid Peroxidation; Lung; Male; Oleic Acids; Plant Oils; Rapeseed Oil; Superoxide Dismutase

Toxic oil syndrome (TOS), characterized by widespread thromboembolism, vasculotoxicity, and ARDS, develops in humans ingesting denatured edible oils. The mechanism(s) involved in targeted vasculocentric damage in this multi-system disorder is not known. Oleylanilide (OA) was synthesized and fed to male, young adult guinea pigs by gavage for 30 days at doses of 35, 50, and 100 mg/kg/day in groups of six animals each respective to weight. Controls were fed olive oil. Oleylanilide fed animals gained less weight than controls. At the end of experiment, right lungs were inflation fixed in appropriate fixative for histology and transmission electron microscopy (TEM) and left lungs were frozen at -70 degrees C for biochemical analyses. The activity of glycerophosphate acyltransferase (GAT) and cholinephosphotransferase (CPT), two key enzymes involved in phospholipid biosynthesis, were decreased in lung due to OA ingestion. All doses of OA induced marked perivascular and peribronchoiolar monocytic infiltrates that often formed prominent nodules; segmental vascular smooth muscle cell proliferation and derangement of myocytic polarity, subendothelial foamy infiltrates, and edema; nuclear pyknosis and dropout in vascular and bronchial targetoid myocytes; and denudation of bronchiolar epithelial cells. Alveoli contained large numbers of monocytes, macrophages, red cells, edema, and debris. Transmission electron microscopy showed type I cell cytoplasmic ballooning and disintegration of type I cell; contracted and blebbed endothelial cells, fibrin thrombi in capillaries, intracellular megalamellar bodies in type II cells, and surfactant lamellae; and liposomes and fine granular precipitates within alveoli, and contraction and lift off of bronchiolar epithelial cells. Monocytes, mast cells, and eosinophils infiltrated bronchial walls. Furthermore, there was deposition of electron dense particles on the surface of the alveolar wall.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Anilides; Animals; Body Weight; Cell Division; Diacylglycerol Cholinephosphotransferase; Disease Models, Animal; Glycerol-3-Phosphate O-Acyltransferase; Guinea Pigs; Lung; Male; Microscopy, Electron; Muscle, Smooth, Vascular; Oleic Acids; Pulmonary Alveoli

The constant injection of [14C]oleylanilide into the vena cava of Wistar rats for 7 days with osmotic minipumps was used to estimate tissue distribution of chronically administered anilides. The largest concentrations of the anilide were found in the brown adipose tissue; all other tissues showed much lower proportions. When anilide distribution was expressed as nmol/g lipid, the high concentration of the compound in the brown adipose tissue contrasted with its very low presence in the white adipose tissue; all other tissues showed intermediate concentrations. Anilide-treated rats consumed more food and lost more weight than did controls; their energy balance showed higher energy inefficiency. The results suggest a possible effect of anilides on the thermogenic pathway of the rat brown adipose tissue. In addition, there was a large individual variability in the proportions of anilide present in all tissues, from as little as 0.3% of the total anilide injected in some animals to 6% in others.

Topics: Adipose Tissue; Adipose Tissue, Brown; Anilides; Animals; Body Weight; Energy Intake; Female; Oleic Acids; Rats; Rats, Wistar; Skin; Tissue Distribution; Venae Cavae

The possible relationship between fatty acid anilides and the toxic oil syndrome (TOS) which appeared in Spain in 1981 has been debated during recent years. These anilides have been detected as anomalous compound in toxic oils analysed. After treatment with one daily dose of 50 mg/kg of oleilanilide (88.86% pure) for 5 days, animals showed a tendency towards progressive loss of body weight and a significant increase in serum concentration of immunoglobulins. The percentage of suppressor T cells in spleen diminished significantly compared with the control group. Consequently, an increase in the helper T cells/suppressor T cells was also observed. The production of IgM and IgG in culture was significantly higher than in controls and no differences were seen in IgA synthesis. The functional studies of generation of specific IgM, IgA and IgG suppressor cells at variable doses of concanavalin A (Con A) showed paradoxical behaviour of suppressor T cells generated by low doses of Con A. A similar change occurred at higher doses of Con A. These results suggest that low-dose treatment with oleilanilides induces an alteration in the immune response in Swiss mice.

Topics: Anilides; Animals; B-Lymphocytes; Body Weight; Cell Count; Cell Differentiation; Concanavalin A; Dose-Response Relationship, Immunologic; Female; Immunity, Innate; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Macrophages; Mice; Oleic Acids; Organ Size; Pokeweed Mitogens; Spleen; T-Lymphocytes; T-Lymphocytes, Regulatory

In the present investigation, we have studied the toxic potential of oleic acid anilide (OAA) and heated oleic acid anilide (HOAA) in relation to the toxic oil syndrome (TOS). Male Sprague-Dawley rats were given 250 mg/kg of OAA or HOAA in mineral oil by gavage, on alternate days for 2 weeks (total 7 doses). The control rats received an equal volume of mineral oil only. The animals were sacrificed at days 1, 7, and 28 following the last dose. Ratio of organ-to-body weight showed increases in spleen and kidney of HOAA and OAA treated rats, respectively, at day 1 while this ratio for liver in HOAA treated group showed a decrease at day 1. Among blood parameters, white blood cells increased in HOAA treated group at day 1 and in both OAA and HOAA groups at day 28. Mean corpuscular hemoglobin (MCH) and mean cell volume (MCV) also showed increases in the HOAA treated rats at days 7 and 28. Serum lactate dehydrogenase (LDH) decreased in both OAA and HOAA treated rats at day 1, while at day 7 the decrease was confined only to the HOAA group. Serum glutamic oxalacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) activities also decreased at most of the time points. Liver mitochondrial ATPase activity decreased in the HOAA group at day 7 and in the OAA group at day 28. Among serum immunoglobulins, IgA levels increased throughout the study but the changes were more pronounced in HOAA treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anilides; Animals; Body Weight; Hot Temperature; Immune System; Male; Oleic Acids; Organ Size; Rats; Rats, Inbred Strains

Topics: Anilides; Animals; Body Weight; Lipids; Male; Oleic Acids; Palmitic Acid; Palmitic Acids; Rats; Rats, Inbred Strains