Crude Heparin Preparations Unveil the Presence of Structurally Diverse Oversulfated Contaminants

Autor(es)

Mendes, Aline ^[1] ; Meneghetti, Maria C. Z. ^[1] ; Palladino, Marcelly Valle ^[1] ; Justo, Giselle Zenker ^{[1, 2]} ; Sassaki, Guilherme L. ^[3] ; Fareed, Jawed ^[4] ; Lima, Marcelo A. ^{[1, 5]} ; Nader, Helena B. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Bioquim, Inst Farmacol & Biol Mol, Escola Paulista Med, Rua Tres Maio 100, BR-04044020 Sao Paulo, SP - Brazil

^[2] Univ Fed Sao Paulo, Dept Ciencias Farmaceut, Campus Diadema, Rua Tres Maio 100, BR-04044020 Sao Paulo, SP - Brazil

^[3] Univ Fed Parana, Dept Bioquim, Setor Ciencias Biol, Ctr Politecn, Ave Coronel Francisco H dos Santos 100, BR-81531980 Curitiba, Parana - Brazil

^[4] Loyola Univ Med Ctr, Dept Mol Pharmacol & Therapeut, Hemostasis & Thrombosis Res Labs, 2160 S First Ave, Maywood, IL 60153 - USA

^[5] Keele Univ, Mol & Struct Biosci, Sch Life Sci, Huxley Bldg, Keele ST5 5BG, Staffs - England

• Tipo de documento: Artigo Científico
• Fonte: Molecules; v. 24, n. 16 AUG 2019.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 17/14179-3 - Tráfego vesicular na biossíntese do heparam sulfato
• Beneficiário: Ivarne Luis dos Santos Tersariol
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/03964-6 - Glicosaminoglicanos e proteoglicanos: relação estrutura e função
• Beneficiário: Helena Bonciani Nader
• Modalidade de apoio: Auxílio à Pesquisa - Temático