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CC BY 4.0 · TH Open 2022; 06(02): e114-e123
DOI: 10.1055/a-1750-1300
Original Article

Pharmacokinetic, Hemostatic, and Anticancer Properties of a Low-Anticoagulant Bovine Heparin

Roberto P. Santos   *
1   Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
,
Ana M.F. Tovar   *
1   Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
,
Marcos R. Oliveira
1   Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
,
Adriana A. Piquet
1   Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
,
Nina V. Capillé
1   Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
,
Stephan N.M.C.G. Oliveira
1   Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
,
Ana H. Correia
2   Hospital Universitário Clementino Fraga Filho, Serviço de Anatomia Patológica, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil
,
José N. Farias
3   Hospital Universitário Clementino Fraga Filho, Laboratório Multidisciplinar de Pesquisa, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil
,
Eduardo Vilanova
1   Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
,
Paulo A.S. Mourão
1   Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
› Author Affiliations Funding This work was supported by the grants 315847/2020-4 from Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq) and E26/290.078/2017 from Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)
› Further Information
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Abstract

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 (approximately 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 heparin (LMWH) enoxaparin and diminished bleeding potential, even at high doses. Subcutaneous treatment with LABH delays 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 in the animals treated with HPI. These results demonstrate that LABH is a promising candidate for prospecting new therapeutic uses for UFH.

Keywords

unfractionated heparin - low-molecular weight heparin - pharmacokinetics - bleeding - Lewis lung carcinoma

Authors' Contributions

A.M.F.T., R.P.S., and P.A.S.M. conceived the research and experimental design; A.M.F.T., R.P.S, A.A.P., M.R.O., N.V.C., S.N.M.C.G.O., J.N.F, and A.H.C conducted the research; A.M.F.T., R.P.S., S.N.M.C.G.O., and E.V. analyzed the data, and R.P.S., A.M.F.T., E.V., and P.A.S.M. wrote the paper.


* These authors contributed equally as first authors.




Publication History

Received: 13 September 2021

Accepted: 20 January 2022

Accepted Manuscript online:
25 January 2022

Article published online:
11 July 2022

© 2022. The Author(s). 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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