Print Email Facebook Twitter Disposition of 14C-α-cyclodextrin in germ-free and conventional rats Title Disposition of 14C-α-cyclodextrin in germ-free and conventional rats Author van Ommen, B. de Bie, A.T.H.J. Bär, A. TNO Voeding Publication year 2004 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 Subject BiologyPhysiological Sciencesalpha cyclodextrincarbon 14alpha cyclodextrin derivativealpha-cyclodextrincarboncyclodextrinanimal experimentanimal tissuearticleblood analysiscarcasscontrolled studydietary fiberfemalefermentationgastrointestinal tractgermfree animalhigh performance liquid chromatographyintestine floraisotope labelingkidney tubule excretionlung alveolus carbon dioxide tensionmalemetabolic regulationnonhumanpriority journalradioisotope distributionratrat strainsmall intestine absorptionspecies comparisonstomach contentanimalblooddrug detoxificationintravenous drug administrationoral drug administrationtissue distributionurineWistar ratMammaliaMicrobiotaRattus norvegicusAdministration, Oralalpha-CyclodextrinsAnimalsCarbon RadioisotopesCyclodextrinsFemaleGerm-Free LifeInjections, IntravenousMaleMetabolic Detoxication, DrugRatsRats, WistarTissue Distribution To reference this document use: http://resolver.tudelft.nl/uuid:732fda3d-e4b7-4b62-b9b6-9b8ba7f24e16 DOI https://doi.org/10.1016/j.yrtph.2004.05.011 TNO identifier 237815 ISSN 0273-2300 Source Regulatory Toxicology and Pharmacology, 39 (SUPPL.) Document type article Files To receive the publication files, please send an e-mail request to TNO Library.