Your browser doesn't support javascript.
loading
Design of anti-inflammatory heparan sulfate to protect against acetaminophen-induced acute liver failure.
Arnold, Katelyn; Xu, Yongmei; Sparkenbaugh, Erica M; Li, Miaomiao; Han, Xiaorui; Zhang, Xing; Xia, Ke; Piegore, Mark; Zhang, Fuming; Zhang, Xiaoxiao; Henderson, Mike; Pagadala, Vijayakanth; Su, Guowei; Tan, Lisi; Park, Pyong Woo; Stravitz, Richard T; Key, Nigel S; Linhardt, Robert J; Pawlinski, Rafal; Xu, Ding; Liu, Jian.
Afiliación
  • Arnold K; Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Xu Y; Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Sparkenbaugh EM; Division of Hematology/Oncology, Department of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Li M; UNC Blood Research Center, University of North Carolina, Chapel Hill, NC 25799, USA.
  • Han X; Department of Oral Biology, School of Dental Medicine, State University of New York at Buffalo, Buffalo, NY 14214, USA.
  • Zhang X; Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
  • Xia K; Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
  • Piegore M; Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
  • Zhang F; Division of Hematology/Oncology, Department of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Zhang X; Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
  • Henderson M; Department of Oral Biology, School of Dental Medicine, State University of New York at Buffalo, Buffalo, NY 14214, USA.
  • Pagadala V; Division of Hematology/Oncology, Department of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Su G; UNC Blood Research Center, University of North Carolina, Chapel Hill, NC 25799, USA.
  • Tan L; Glycan Therapeutics, LLC, Raleigh, NC 27606, USA.
  • Park PW; Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Stravitz RT; Department of Oral Biology, School of Dental Medicine, State University of New York at Buffalo, Buffalo, NY 14214, USA.
  • Key NS; Department of Periodontics, School of Stomatology, China Medical University, Shenyang, Liaoning 110002, China.
  • Linhardt RJ; Division of Respiratory Diseases, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Division of Newborn Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Pawlinski R; Hume-Lee Transplant Center of Virginia Commonwealth University, Richmond, VA 23219, USA.
  • Xu D; Division of Hematology/Oncology, Department of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Liu J; UNC Blood Research Center, University of North Carolina, Chapel Hill, NC 25799, USA.
Sci Transl Med ; 12(535)2020 03 18.
Article en En | MEDLINE | ID: mdl-32188725
Acetaminophen/paracetamol (APAP) overdose is the leading cause of drug-induced acute liver failure (ALF) in the United States and Europe. The progression of the disease is attributed to sterile inflammation induced by the release of high mobility group box 1 (HMGB1) and the interaction with receptor for advanced glycation end products (RAGE). A specific, effective, and safe approach to neutralize the proinflammatory activity of HMGB1 is highly desirable. Here, we found that a heparan sulfate (HS) octadecasaccharide (18-mer-HP or hepatoprotective 18-mer) displays potent hepatoprotection by targeting the HMGB1/RAGE axis. Endogenous HS proteoglycan, syndecan-1, is shed in response to APAP overdose in mice and humans. Furthermore, purified syndecan-1, but not syndecan-1 core protein, binds to HMGB1, suggesting that HMGB1 binds to HS polysaccharide side chains of syndecan-1. Last, we compared the protection effect between 18-mer-HP and N-acetyl cysteine, which is the standard of care to treat APAP overdose. We demonstrated that 18-mer-HP administered 3 hours after a lethal dose of APAP is fully protective; however, the treatment of N-acetyl cysteine loses protection. Therefore, 18-mer-HP may offer a potential therapeutic advantage over N-acetyl cysteine for late-presenting patients. Synthetic HS provides a potential approach for the treatment of APAP-induced ALF.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fallo Hepático Agudo / Enfermedad Hepática Inducida por Sustancias y Drogas Límite: Animals / Humans País/Región como asunto: Europa Idioma: En Revista: Sci Transl Med Asunto de la revista: CIENCIA / MEDICINA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fallo Hepático Agudo / Enfermedad Hepática Inducida por Sustancias y Drogas Límite: Animals / Humans País/Región como asunto: Europa Idioma: En Revista: Sci Transl Med Asunto de la revista: CIENCIA / MEDICINA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos