Comparative studies of heparin and heparin fragments: distribution and toxicity in the rat.
To control blood levels of heparin during extracorporeal therapy, the use of a blood filter containing heparinase, a heparin-specific enzyme that cleaves heparin to small fragments with less anticoagulant activity, has been proposed. These fragments have anti-factor Xa activity but no anti-thrombin activity. The potential toxicity of heparin fragments as compared to heparin was examined in rats by identifying presumptive sites of drug-related toxicity by whole-body autoradiography and by histological examination of major organs. Radioautograms of rats sacrificed 5 hr after dosing with [35S]heparin fragments indicated no potential targets different from what was observed in rats dosed with [35S]heparin. In addition, the faster urinary clearance of heparin fragments resulted in a lower concentration of these fragments than of heparin in all common target organs. No hemorrhages or other lesions were found in rats injected intravenously with heparin fragments (100 mg/kg) and sacrificed after 5 hr. In addition, no mortality or delayed toxic effects were observed in a similar group of animals sacrificed 2 weeks after dosing. In contrast, 80% of rats injected with heparin (100 mg/kg) showed hemorrhages of the lungs at the time of necropsy.
D000818:Animals; D001345:Autoradiography; D006493:Heparin / Q000378:metabolism* / Q000633:toxicity; D019763:Heparin Lyase; D008297:Male; D011133:Polysaccharide-Lyases; D051381:Rats; D011919:Rats, Inbred Strains; D013462:Sulfur Radioisotopes; D013552:Swine; D014018:Tissue Distribution
D013462:Sulfur Radioisotopes; D006493:Heparin; D011133:Polysaccharide-Lyases; D019763:Heparin Lyase