A Mendes
Crude Heparin Preparations Unveil the Presence of Structurally Diverse Oversulfated Contaminants
Mendes, A; Meneghetti, MCZ; Palladino, MV; Justo, GZ; Sassaki, GL; Fareed, J; Andrade De Lima, M; Nader, HB
Authors
MCZ Meneghetti
MV Palladino
GZ Justo
GL Sassaki
J Fareed
Marcelo Andrade De Lima m.andrade.de.lima@keele.ac.uk
HB Nader
Abstract
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.
Citation
Mendes, A., Meneghetti, M., Palladino, M., Justo, G., Sassaki, G., Fareed, J., …Nader, H. (2019). Crude Heparin Preparations Unveil the Presence of Structurally Diverse Oversulfated Contaminants. Molecules, 24, 2988--2988. https://doi.org/10.3390/molecules24162988
Journal Article Type | Article |
---|---|
Acceptance Date | Aug 10, 2019 |
Publication Date | Aug 17, 2019 |
Journal | Molecules |
Electronic ISSN | 1420-3049 |
Publisher | MDPI |
Volume | 24 |
Pages | 2988--2988 |
DOI | https://doi.org/10.3390/molecules24162988 |
Keywords | 1H NMR and COSY, FACE, heparin and oversulfated chondroitin sulfate anticoagulant activities, heparinases, oversulfated chondroitin sulfate |
Publisher URL | https://doi.org/10.3390/molecules24162988 |
Files
molecules-24-02988-v2.pdf
(4.1 Mb)
PDF
Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/
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