title: The fate of ingested glyceran esters of condensed castor oil fatty acids [polyglycerol polyricinoleate (PGPR)] in the rat.
abstract: Samples of the emulsifier polyglycerol polyricinoleate (PGPR) were synthesized using the radiolabelled precursors [1-14C]glycerol ([14C]polyglycerol PGPR), [9,10-3H] or [12-3H]ricinoleic acid ([3H] PGPR) or [1-14C]stearic acid ([14C]stearyl PGPR). The absorption, tissue distribution, metabolism and excretion of these 14C- or tritium-labelled PGPR samples administered to rats was studied. The effects of intestinal and porcine pancreatic lipases on PGPR preparations were examined. Rats were dosed with [1-14C]glycerol, [14C]polyglycerol and ([14C]polyglycerol)PGPR by gavage and their urine. faeces and expired CO2 monitored for 14C. The results from the [1-14C]glycerol treated animals showed extensive metabolism of glycerol. For [14C]polyglycerols, the lower polyglycerols were preferentially absorbed from the intestine and were excreted unchanged in the urine while the higher polyglycerols were found in the faeces. After 4 days, 93% of the dose of polyglycerols was recovered, of which some 30% was found in the urine and 60% in the faeces. Traces of 14C activity were found in depot fat and liver. The excretory pattern and urinary metabolites from ([14C]polyglycerol) PGPR was very similar to that of [14C]polyglycerol. Analysis of urinary and faecal 14C material indicated that the PGPR polymer was digested to give free polyglycerol and polyricinoleic acid. PGPR was synthesised incorporating [1-14C]stearic into polyricinoleic acid which was then esterified with polyglycerol. The resulting [14C]PGPR or [1-14C] stearic acid in a dietary slurry was administered to groups of fed or starved rats by gavage. The results indicated complete digestion of PGPR and absorption of the fatty acids. The 14C-material absorbed was extensively laid down in depot fat and some metabolism to 14CO2 was demonstrated. The fate of the stearic acid was similar whether dosed alone or incorporated into the PGPR polymer. Samples of PGPR were synthesized containing 3H-labelled ricinoleic acid. The resulting [3H]PGPR was intubated into rats as a component of a dietary slurry. The results indicated that the polymer is extensively digested and 90% of the administered tritium is absorbed. The absorbed material was extensively metabolized within 24 hr so that large amounts of tritium were present in the aqueous phase of the tissues examined. After 24 hr, less than 5% of the administered material was present as lipid material, of which a large proportion was as non-hydroxy fatty acids. No traces of polymer material were found in the tissues examined. In vitro digestion of PGPR by porcine pancreatic lipase and rat intestinal fractions was demonstrated. The results indicate very extensive digestion of the PGPR polymer to polyglycerols and fatty acids. The fatty acids are metabolized extensively. The mono-, di- and triglycerols are extensively absorbed from the intestinal tract and rapidly excreted in the urine unchanged but the hexa-, penta- and higher polyglycerols are essentially not absorbed and excreted in the faeces unchanged.
authors.affiliation: Environmental Safety Laboratory, Unilever Research, Sharnbrook, Bedford, UK.
authors.forename: D
authors.initials: D
authors.lastname: Howes
authors.forename: R
authors.initials: R
authors.lastname: Wilson
authors.forename: C T
authors.initials: CT
authors.lastname: James
mesh_terms: D000818:Animals; D001944:Breath Tests; D002250:Carbon Radioisotopes; D002855:Chromatography, Thin Layer; D005227:Fatty Acids / Q000302:isolation & purification / Q000378:metabolism; D005243:Feces / Q000737:chemistry; D005503:Food Additives; D005990:Glycerol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000493:pharmacokinetics / Q000652:urine; D007408:Intestinal Absorption; D008049:Lipase; D008297:Male; D011108:Polymers / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012277:Ricinoleic Acids / Q000138:chemical synthesis / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D013229:Stearic Acids / Q000378:metabolism; D013501:Surface-Active Agents; D014018:Tissue Distribution; D014316:Tritium
chemical_list: D002250:Carbon Radioisotopes; D005227:Fatty Acids; D005503:Food Additives; D011108:Polymers; D012277:Ricinoleic Acids; D013229:Stearic Acids; D013501:Surface-Active Agents; C029243:glyceran polyricinoleic acid ester; D014316:Tritium; C043941:polyglycerol; C031183:stearic acid; D008049:Lipase; C030521:ricinoleic acid; D005990:Glycerol