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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Vydané v:Molecules (Basel, Switzerland) Ročník 24; číslo 16; s. 2988
Hlavní autori: Mendes, Aline, Meneghetti, Maria C. Z., Palladino, Marcelly Valle, Justo, Giselle Zenker, Sassaki, Guilherme L., Fareed, Jawed, Lima, Marcelo A., Nader, Helena B.
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: Switzerland MDPI AG 17.08.2019
MDPI
Predmet:
1H NMR and COSY
Acids
Animals
Anticoagulants
Anticoagulants - chemistry
Anticoagulants - isolation & purification
Cattle
Chondroitin sulfate
Chondroitin Sulfates - chemistry
Chondroitin Sulfates - isolation & purification
Chromatography
Drug Contamination
Enzymes
FACE
Heparan sulfate
Heparin - chemistry
Heparin - isolation & purification
heparin and oversulfated chondroitin sulfate anticoagulant activities
Heparin Lyase - chemistry
heparinases
Humans
Hydrolysis
Intestinal Mucosa - chemistry
Magnetic Resonance Spectroscopy
NMR
Nuclear magnetic resonance
oversulfated chondroitin sulfate
Polysaccharide-Lyases - chemistry
Quality Control
Spectrum analysis
Swine
China
heparin and oversulfated chondroitin sulfate anticoagulant activities
heparinases
oversulfated chondroitin sulfate
1H NMR and COSY
FACE
ISSN:1420-3049, 1420-3049
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Popis
Shrnutí: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.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:1420-3049
1420-3049
DOI:10.3390/molecules24162988