Tissue Distribution and Antithrombotic Activity of Unlabeled or 14C-Labelled Porcine Intestinal Mucosal Heparin Following Administration to Rats by the Oral Route
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Authors
Hiebert, Linda M.
Wice, Sandra M.
Ping, Tilly
Hileman, Ronald E.
Capila, Ishan
Linhardt, Robert J.
Issue Date
2000-01-01
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
Distribution and antithrombotic activity of orally administered unfractionated porcine heparin were studied. [14C]Heparin was prepared by de-N-acetylation of porcine mucosal heparin followed by re-N-acetylation, using [14C]acetic anhydride. [14C]Heparin and (or) cold heparin (60 mg/kg) were administered by stomach tube to male Wistar rats. Blood, all levels of gut and gut contents, liver, lung, spleen, kidney, and aortic and vena caval endothelium were collected under deep anesthesia at 3, 6, 15, 30, and 60 min and 4 and 24 h (6 rats/group) after administration. Urine and feces were collected at 24 h, using metabolic cages. In three additional rats, drugs were administered in gelatin capsules. Tissues listed above and tongue, esophagus, trachea, brain, heart, thymus, bile ducts, vena caval and aortic walls, ureters, bladder, samples of muscle, skin, hair, and bone marrow were collected at 24 h. Radioactivity and chemical heparin, measured by agarose gel electrophoresis, were observed in all tissues examined as well as gut washes, plasma, urine, and feces. Radiolabel recovered was confirmed to be heparin by autoradiograms of gradient polyacrylamide electrophoretic gels. [14C]Heparin and chemical heparin in gut tissue suggest a transit time of 4 h. Porcine or bovine heparin (7.5 mg/kg), administered by stomach tube, decreased the incidence of thrombosis induced by applying 10% formalin in 65% methanol to the exposed jugular vein of rats. Heparin isolation from non-gut tissue, endothelium, urine, and plasma and the observed antithrombotic effect are consistent with oral bioavailability.
Description
Canadian Journal of Physiology and Pharmacology, 78, 307-320
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Full Citation
Tissue Distribution and Antithrombotic Activity of Unlabeled or 14C-Labelled Porcine Intestinal Mucosal Heparin Following Administration to Rats by the Oral Route, L.M. Hiebert, S.M. Wice, T. Ping, R.E. Hileman, I. Capila, R.J. Linhardt, Canadian Journal of Physiology and Pharmacology, 78, 307-320, 2000.
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Journal
Volume
Issue
PubMed ID
DOI
ISSN
84212