Howes D, Wilson R, James C T
Environmental Safety Laboratory, Unilever Research, Sharnbrook, Bedford, UK.
Food Chem Toxicol. 1998 Sep-Oct;36(9-10):719-38. doi: 10.1016/s0278-6915(98)00055-6.
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.
使用放射性标记的前体[1-¹⁴C]甘油([¹⁴C]聚甘油聚蓖麻醇酸酯)、[9,10-³H]或[12-³H]蓖麻油酸([³H]聚甘油聚蓖麻醇酸酯)或[1-¹⁴C]硬脂酸([¹⁴C]硬脂酰聚甘油聚蓖麻醇酸酯)合成乳化剂聚甘油聚蓖麻醇酸酯(PGPR)样品。研究了给大鼠施用这些¹⁴C或氚标记的PGPR样品后的吸收、组织分布、代谢和排泄情况。检测了肠脂肪酶和猪胰脂肪酶对PGPR制剂的作用。通过灌胃给大鼠施用[1-¹⁴C]甘油、[¹⁴C]聚甘油和([¹⁴C]聚甘油)PGPR,并监测它们的尿液、粪便和呼出的二氧化碳中的¹⁴C。[1-¹⁴C]甘油处理组动物的结果显示甘油有广泛的代谢。对于[¹⁴C]聚甘油,较低的聚甘油优先从肠道吸收并原样排泄到尿液中,而较高的聚甘油则存在于粪便中。4天后,回收了93%的聚甘油剂量,其中约30%在尿液中发现,60%在粪便中发现。在储存脂肪和肝脏中发现了微量的¹⁴C活性。([¹⁴C]聚甘油)PGPR的排泄模式和尿液代谢物与[¹⁴C]聚甘油非常相似。对尿液和粪便中¹⁴C物质的分析表明,PGPR聚合物被消化产生游离的聚甘油和聚蓖麻油酸。将[1-¹⁴C]硬脂酸掺入聚蓖麻油酸中合成PGPR,然后将其与聚甘油酯化。将所得的[¹⁴C]PGPR或膳食浆液中的[1-¹⁴C]硬脂酸通过灌胃给予喂食或饥饿的大鼠组。结果表明PGPR完全被消化且脂肪酸被吸收。吸收的¹⁴C物质大量沉积在储存脂肪中,并显示出一些代谢为¹⁴CO₂的情况。无论单独给药还是掺入PGPR聚合物中,硬脂酸的命运都是相似的。合成了含有³H标记蓖麻油酸的PGPR样品。将所得的[³H]PGPR作为膳食浆液的成分插管给大鼠。结果表明该聚合物被广泛消化,90%的施用氚被吸收。吸收的物质在24小时内被广泛代谢,以至于在所检查组织的水相中存在大量的氚。24小时后,施用物质中不到5%以脂质物质形式存在,其中很大一部分是非羟基脂肪酸。在所检查的组织中未发现聚合物物质的痕迹。证明了猪胰脂肪酶和大鼠肠部分对PGPR的体外消化。结果表明PGPR聚合物被非常广泛地消化为聚甘油和脂肪酸。脂肪酸被广泛代谢。单甘油酯、二甘油酯和三甘油酯从肠道被广泛吸收并原样迅速排泄到尿液中,但六甘油酯、五甘油酯和更高的聚甘油基本上不被吸收并原样排泄到粪便中。