PMID- 35707626 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220918 IS - 2512-9465 (Electronic) IS - 2567-3459 (Print) IS - 2512-9465 (Linking) VI - 6 IP - 2 DP - 2022 Apr TI - Pharmacokinetic, Hemostatic, and Anticancer Properties of a Low-Anticoagulant Bovine Heparin. PG - e114-e123 LID - 10.1055/s-0042-1745743 [doi] AB - 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. CI - 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/ ). FAU - Santos, Roberto P AU - Santos RP AD - Hospital Universitario Clementino Fraga Filho and Instituto de Bioquimica Medica Leopoldo de Meis, Laboratorio de Tecido Conjuntivo, Hospital Universitario Clementino Fraga Filho and Instituto de Bioquimica Medica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Tovar, Ana M F AU - Tovar AMF AD - Hospital Universitario Clementino Fraga Filho and Instituto de Bioquimica Medica Leopoldo de Meis, Laboratorio de Tecido Conjuntivo, Hospital Universitario Clementino Fraga Filho and Instituto de Bioquimica Medica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Oliveira, Marcos R AU - Oliveira MR AD - Hospital Universitario Clementino Fraga Filho and Instituto de Bioquimica Medica Leopoldo de Meis, Laboratorio de Tecido Conjuntivo, Hospital Universitario Clementino Fraga Filho and Instituto de Bioquimica Medica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Piquet, Adriana A AU - Piquet AA AD - Hospital Universitario Clementino Fraga Filho and Instituto de Bioquimica Medica Leopoldo de Meis, Laboratorio de Tecido Conjuntivo, Hospital Universitario Clementino Fraga Filho and Instituto de Bioquimica Medica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Capille, Nina V AU - Capille NV AD - Hospital Universitario Clementino Fraga Filho and Instituto de Bioquimica Medica Leopoldo de Meis, Laboratorio de Tecido Conjuntivo, Hospital Universitario Clementino Fraga Filho and Instituto de Bioquimica Medica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Oliveira, Stephan N M C G AU - Oliveira SNMCG AD - Hospital Universitario Clementino Fraga Filho and Instituto de Bioquimica Medica Leopoldo de Meis, Laboratorio de Tecido Conjuntivo, Hospital Universitario Clementino Fraga Filho and Instituto de Bioquimica Medica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Correia, Ana H AU - Correia AH AD - Hospital Universitario Clementino Fraga Filho, Servico de Anatomia Patologica, Hospital Universitario Clementino Fraga Filho, Rio de Janeiro, Brazil. FAU - Farias, Jose N AU - Farias JN AD - Hospital Universitario Clementino Fraga Filho, Laboratorio Multidisciplinar de Pesquisa, Hospital Universitario Clementino Fraga Filho, Rio de Janeiro, Brazil. FAU - Vilanova, Eduardo AU - Vilanova E AD - Hospital Universitario Clementino Fraga Filho and Instituto de Bioquimica Medica Leopoldo de Meis, Laboratorio de Tecido Conjuntivo, Hospital Universitario Clementino Fraga Filho and Instituto de Bioquimica Medica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Mourao, Paulo A S AU - Mourao PAS AD - Hospital Universitario Clementino Fraga Filho and Instituto de Bioquimica Medica Leopoldo de Meis, Laboratorio de Tecido Conjuntivo, Hospital Universitario Clementino Fraga Filho and Instituto de Bioquimica Medica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. LA - eng PT - Journal Article DEP - 20220526 PL - Germany TA - TH Open JT - TH open : companion journal to thrombosis and haemostasis JID - 101715740 PMC - PMC9135479 OTO - NOTNLM OT - Lewis lung carcinoma OT - bleeding OT - low-molecular weight heparin OT - pharmacokinetics OT - unfractionated heparin COIS- Conflict of Interest None declared. EDAT- 2022/06/17 06:00 MHDA- 2022/06/17 06:01 PMCR- 2022/07/01 CRDT- 2022/06/16 02:42 PHST- 2021/09/13 00:00 [received] PHST- 2022/01/20 00:00 [accepted] PHST- 2022/06/16 02:42 [entrez] PHST- 2022/06/17 06:00 [pubmed] PHST- 2022/06/17 06:01 [medline] PHST- 2022/07/01 00:00 [pmc-release] AID - 210072 [pii] AID - 10.1055/s-0042-1745743 [doi] PST - epublish SO - TH Open. 2022 May 26;6(2):e114-e123. doi: 10.1055/s-0042-1745743. eCollection 2022 Apr.