Crude Heparin Preparations Unveil the Presence of Structurally Diverse Oversulfated Contaminants
Nowadays, pharmaceutical heparin is purified from porcine and bovine intestinal mucosa. In the past decade there has been an ongoing concern about the safety of heparin, since in 2008, adverse effects associated with the presence of an oversulfated chondroitin sulfate (OSCS) were observed in prepara...
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doaj-2fcde83ade774ddaa2768c68f2d10f0e2020-11-25T02:17:12ZengMDPI AGMolecules1420-30492019-08-012416298810.3390/molecules24162988molecules24162988Crude Heparin Preparations Unveil the Presence of Structurally Diverse Oversulfated ContaminantsAline Mendes0Maria C. Z. Meneghetti1Marcelly Valle Palladino2Giselle Zenker Justo3Guilherme L. Sassaki4Jawed Fareed5Marcelo A. Lima6Helena B. Nader7Departamento de Bioquímica, Instituto de Farmacologia e Biologia Molecular, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Três de Maio, 100 – São Paulo, SP 04044-020, BrazilDepartamento de Bioquímica, Instituto de Farmacologia e Biologia Molecular, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Três de Maio, 100 – São Paulo, SP 04044-020, BrazilDepartamento de Bioquímica, Instituto de Farmacologia e Biologia Molecular, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Três de Maio, 100 – São Paulo, SP 04044-020, BrazilDepartamento de Bioquímica, Instituto de Farmacologia e Biologia Molecular, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Três de Maio, 100 – São Paulo, SP 04044-020, BrazilDepartamento de Bioquímica, Setor de Ciências Biológicas, Centro Politécnico, Universidade Federal do Paraná, Avenida Coronel Francisco H. dos Santos, 100, Caixa Postal 19031, Curitiba, PR 81531-980, BrazilDepartment of Molecular Pharmacology & Therapeutics, Hemostasis & Thrombosis Research Laboratories, Loyola University Medical Center, 2160 S. First Avenue Maywood, IL 60153, USADepartamento de Bioquímica, Instituto de Farmacologia e Biologia Molecular, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Três de Maio, 100 – São Paulo, SP 04044-020, BrazilDepartamento de Bioquímica, Instituto de Farmacologia e Biologia Molecular, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Três de Maio, 100 – São Paulo, SP 04044-020, BrazilNowadays, pharmaceutical heparin is purified from porcine and bovine intestinal mucosa. In the past decade there has been an ongoing concern about the safety of heparin, since in 2008, adverse effects associated with the presence of an oversulfated chondroitin sulfate (OSCS) were observed in preparations of pharmaceutical porcine heparin, which led to the death of patients, causing a global public health crisis. However, it has not been clarified whether OSCS has been added to the purified heparin preparation, or whether it has already been introduced during the production of the raw heparin. Using a combination of different analytical methods, we investigate both crude and final heparin products and we are able to demonstrate that the sulfated contaminants are intentionally introduced in the initial steps of heparin preparation. Furthermore, the results show that the oversulfated compounds are not structurally homogeneous. In addition, we show that these contaminants are able to bind to cells in using well known heparin binding sites. Together, the data highlights the importance of heparin quality control even at the initial stages of its production.https://www.mdpi.com/1420-3049/24/16/2988oversulfated chondroitin sulfateheparin and oversulfated chondroitin sulfate anticoagulant activities<sup>1</sup>H NMR and COSYFACEheparinases |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Aline Mendes Maria C. Z. Meneghetti Marcelly Valle Palladino Giselle Zenker Justo Guilherme L. Sassaki Jawed Fareed Marcelo A. Lima Helena B. Nader |
spellingShingle |
Aline Mendes Maria C. Z. Meneghetti Marcelly Valle Palladino Giselle Zenker Justo Guilherme L. Sassaki Jawed Fareed Marcelo A. Lima Helena B. Nader Crude Heparin Preparations Unveil the Presence of Structurally Diverse Oversulfated Contaminants Molecules oversulfated chondroitin sulfate heparin and oversulfated chondroitin sulfate anticoagulant activities <sup>1</sup>H NMR and COSY FACE heparinases |
author_facet |
Aline Mendes Maria C. Z. Meneghetti Marcelly Valle Palladino Giselle Zenker Justo Guilherme L. Sassaki Jawed Fareed Marcelo A. Lima Helena B. Nader |
author_sort |
Aline Mendes |
title |
Crude Heparin Preparations Unveil the Presence of Structurally Diverse Oversulfated Contaminants |
title_short |
Crude Heparin Preparations Unveil the Presence of Structurally Diverse Oversulfated Contaminants |
title_full |
Crude Heparin Preparations Unveil the Presence of Structurally Diverse Oversulfated Contaminants |
title_fullStr |
Crude Heparin Preparations Unveil the Presence of Structurally Diverse Oversulfated Contaminants |
title_full_unstemmed |
Crude Heparin Preparations Unveil the Presence of Structurally Diverse Oversulfated Contaminants |
title_sort |
crude heparin preparations unveil the presence of structurally diverse oversulfated contaminants |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2019-08-01 |
description |
Nowadays, pharmaceutical heparin is purified from porcine and bovine intestinal mucosa. In the past decade there has been an ongoing concern about the safety of heparin, since in 2008, adverse effects associated with the presence of an oversulfated chondroitin sulfate (OSCS) were observed in preparations of pharmaceutical porcine heparin, which led to the death of patients, causing a global public health crisis. However, it has not been clarified whether OSCS has been added to the purified heparin preparation, or whether it has already been introduced during the production of the raw heparin. Using a combination of different analytical methods, we investigate both crude and final heparin products and we are able to demonstrate that the sulfated contaminants are intentionally introduced in the initial steps of heparin preparation. Furthermore, the results show that the oversulfated compounds are not structurally homogeneous. In addition, we show that these contaminants are able to bind to cells in using well known heparin binding sites. Together, the data highlights the importance of heparin quality control even at the initial stages of its production. |
topic |
oversulfated chondroitin sulfate heparin and oversulfated chondroitin sulfate anticoagulant activities <sup>1</sup>H NMR and COSY FACE heparinases |
url |
https://www.mdpi.com/1420-3049/24/16/2988 |
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