Absorption and effects of 3-(N-phenylamino)-1,2-propanediol esters in relation to toxic oil syndrome.
Toxic Oil Syndrome (TOS) was an epidemic disease related to the consumption of rapeseed oil denatured with aniline that made its sudden appearance in Spain in 1981. The fatty acid esters of 3-(N-phenylamino)-1,2-propanediol (PAP), which is a chemical class of by-products resulting from the reaction of aniline with oil components, have shown a strong association with TOS-related oils. These compounds also show some structural similarities to platelet-activating factor (PAF). In search of a toxic agent that could explain the widespread systemic effects observed in TOS patients, we investigated the intestinal absorption and biotransformation of the different PAP esters found in TOS-related oil samples and the possible pathophysiological effect of these mediators and their metabolic products if acting as PAF analogs. Results indicate that PAP esters are absorbed in the gastrointestinal tract and are distributed and stored in different organs, particularly in the liver and brown adipose tissue. PAP in these organs showed different patterns of fatty acids, indicating the ability of the gastrointestinal tract to modify the fatty acid composition of the parent PAP. Thus, the fatty acid profile of the PAP esters found in intestine appears to be related to the type of oil used as vehicle. Some of these PAP esters, when a long acyl chain was present in the sn-1 position of the molecule, showed an inhibitory effect on the PAF synthesis. This is an important observation in line with the systemic nature of the disease.
Closa
D
D
Department of Medical Bioanalysis, Institut d'Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones Científicas, Spain.
Folch
E
E
Calaf
R E
RE
Abián
J
J
Roselló-Catafau
J
J
Gelpí
E
E
D000273:Adipose Tissue / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000378:metabolism; D000814:Aniline Compounds / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002250:Carbon Radioisotopes; D004075:Diglycerides / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004952:Esters / Q000493:pharmacokinetics* / Q000494:pharmacology*; D005229:Fatty Acids, Monounsaturated; D007408:Intestinal Absorption; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010938:Plant Oils / Q000633:toxicity*; D010972:Platelet Activating Factor / Q000096:biosynthesis; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011409:Propylene Glycols / Q000493:pharmacokinetics / Q000494:pharmacology; D000074262:Rapeseed Oil; D051381:Rats; D017208:Rats, Wistar; D013577:Syndrome; D014018:Tissue Distribution; D014316:Tritium
D000814:Aniline Compounds; D002250:Carbon Radioisotopes; D004075:Diglycerides; D004952:Esters; D005229:Fatty Acids, Monounsaturated; D008070:Lipopolysaccharides; D010938:Plant Oils; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D011409:Propylene Glycols; D000074262:Rapeseed Oil; D014316:Tritium; C092834:3-(N-phenylamino)-1,2-propanediol 1-oleoyl ester