Repository hosted by TU Delft Library

Home · Contact · About · Disclaimer ·
 

Disposition of 14C-α-cyclodextrin in germ-free and conventional rats

Publication files not online:

Author: Ommen, B. van · Bie, A.T.H.J. de · Bär, A.
Type:article
Date:2004
Institution: TNO Voeding
Source:Regulatory Toxicology and Pharmacology, SUPPL., 39
Identifier: 237815
doi: doi:10.1016/j.yrtph.2004.05.011
Keywords: Biology · Physiological Sciences · alpha cyclodextrin · carbon 14 · alpha cyclodextrin derivative · alpha-cyclodextrin · carbon · cyclodextrin · animal experiment · animal tissue · article · blood analysis · carcass · controlled study · dietary fiber · female · fermentation · gastrointestinal tract · germfree animal · high performance liquid chromatography · intestine flora · isotope labeling · kidney tubule excretion · lung alveolus carbon dioxide tension · male · metabolic regulation · nonhuman · priority journal · radioisotope distribution · rat · rat strain · small intestine absorption · species comparison · stomach content · animal · blood · drug detoxification · intravenous drug administration · oral drug administration · tissue distribution · urine · Wistar rat · Mammalia · Microbiota · Rattus norvegicus · Administration, Oral · alpha-Cyclodextrins · Animals · Carbon Radioisotopes · Cyclodextrins · Female · Germ-Free Life · Injections, Intravenous · Male · Metabolic Detoxication, Drug · Rats · Rats, Wistar · Tissue Distribution

Abstract

The absorption, disposition, metabolism, and excretion of uniformly 14C-labeled α-cyclodextrin (14C-α-CD) was examined in four separate experiments with Wistar rats. In Experiment 1, 14C-α-CD (25μCi, 50mg/kg bw) was administered intravenously to four male and four female conventional rats. In Experiment 2, 14C-α-CD (25μCi, 200mg/kg bw) was given by gavage to four male and four female germ-free rats. In Experiments 3 and 4, 14C-α-CD was given to groups of four male and four female conventional rats by gavage at different dose levels (100μCi, 200mg/kg bw; 25μCi, 200 and 100mg/kg bw). In all experiments, 14C was measured in respiratory CO2, urine, and feces over periods of 24-48h, and in the contents of the gastrointestinal tract, blood, main organs, and residual carcass at termination of the experiments. The chemical identity of the 14C-labeled compounds was examined by HPLC in blood (Experiment 1), urine (Experiments 1-4), feces (Experiments 2-4), and samples of intestinal contents (Experiments 2 and 4). Recovered 14C was expressed as percentage of the administered dose. Experiment 1 showed that intravenously administered α-CD is excreted rapidly with urine. During the first 2h after dosing, plasma 14C levels decreased rapidly (t1/2, 26 and 21min in male and female rats, respectively). About 13% of the administered 14C dose (range 4.6-30.6) was detected in the feces, respiratory CO2, organs, and carcass at the end of the experiment, i.e., 24h after dosing. The presence of about 1.9% in the intestinal contents and feces suggests that a certain fraction of systemic α-CD is eliminated with the bile or saliva. Conclusive evidence, either positive or negative, for a hydrolysis and further metabolism of a small fraction of the administered α-CD by the enzymes of the mammalian body could not be gained from this experiment. Upon oral administration of 14C-α-CD to germ-free rats (Experiment 2), about 1.3% of the label expired as CO2 within 24h. In the urine collected from 0 to 8h after dosing, 14C-α-CD was the only radiolabeled compound detected. The amounts of α-CD detected in the urine suggest that on average about 1% of an oral dose is absorbed in rats during small-intestinal passage. In conventional rats (Experiments 3 and 4), a delayed appearance of respiratory 14CO2 was observed which is attributed to the non-digestibility of α-CD and its subsequent microbial fermentation in the cecum and colon. In the urine collected at 4h after dosing, a small amount of unchanged 14C-α-CD was detected which confirms that about 1% of the ingested α-CD is absorbed intact and is excreted via the kidneys. No 14C-α-CD was found in the feces. It is concluded from the data that ingested 14C-α-CD is not digested in the small intestine of rats but is fermented completely by the intestinal microbiota to absorbable short-chain fatty acids. Therefore, the metabolism of α-CD resembles closely that of resistant starch or other fermentable dietary fibers. © 2004 Elsevier Inc. All rights reserved. Chemicals / CAS: alpha cyclodextrin, 10016-20-3; carbon 14, 14762-75-5; carbon, 7440-44-0; cyclodextrin, 12619-70-4; alpha-cyclodextrin, 10016-20-3; alpha-Cyclodextrins; Carbon Radioisotopes; Cyclodextrins