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Pharmacokinetic, hemostatic and anticancer properties of a low-anticoagulant bovine heparinLow-anticoagulant bovine heparin pharmacological properties
Heparin is a centennial anticoagulant drug broadly employed for treatment and prophylaxis of thromboembolic conditions. Although unfractionated heparin (UFH) has already been shown to have remarkable pharmacological potential for treating a variety of diseases unrelated with thromboembolism, including cancer, atherosclerosis, inflammation and virus infections, its high anticoagulant potency makes the doses necessary to exert non-hemostatic effects unsafe due to an elevated bleeding risk. Our group recently developed a new low-anticoagulant bovine heparin (LABH) bearing the same disaccharide building blocks of the UFH gold standard sourced from porcine mucosa (HPI) but with anticoagulant potency approximately 85% lower (~25 and ~180 Heparin International Units [IU]/mg). In the present work we investigated the pharmacokinetics profile, bleeding potential and anticancer properties of LABH administered subcutaneous into mice. LABH showed pharmacokinetics profile similar to HPI but different from the low-molecular-weight (LMWH) enoxaparin and diminished bleeding potential, even at high doses. Subcutaneous treatment with LABH delayed the early progression of Lewis lung carcinoma, improves survival and brings beneficial health outcomes to the mice, without the advent of adverse effects (hemorrhage/mortality) seen to the animals treated with HPI. These results demonstrate that LABH is a promising candidate for prospecting new therapeutic uses for UFH.
Received: 06 October 2021
Accepted after revision: 20 January 2022
Accepted Manuscript online:
25 January 2022
© 2022. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).
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