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A new heparin fragment decreases liver ischemia-reperfusion injury |
Enio R Vasques a , Estela RR Figueira a , b , ∗, Joel A Rocha-Filho a , c , Cinthia Lanchotte a , Jorge LS Ximenes a , c , Helena B Nader d , Ivarne LS Tersariol d , Marcelo A Lima d , Tiago Rodrigues e , Jose EM Cunha a , b , Eleazar Chaib a , f , Luiz AC D’Albuquerque a , f , Flavio HF Galvao a , f |
a Laboratorio de Investigaçao Medica 37, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao
Paulo, Sao Paulo 01246-903, Brazil
b Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
c Disciplina de Anestesiologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
d Departamento de Bioquimica, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
e Universidade Federal do ABC, Santo Andre, Sao Paulo, Brazil
f Servico de Transplante de Figado e Orgaos do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas HCFMUSP, Faculdade de
Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
∗ Corresponding author at: Hospital das Clinicas of University of Sao Paulo School of Medicine, Department of Gastroenterology, Av Dr Arnaldo, 455, 3rd floor, LIM-37 - office 3222, Zip code: 01246-903, Sao Paulo, SP, Brazil.
E-mail addresses: estela.figueira@hc.fm.usp.br , estelafigueira@me.com (E.R. Figueira). |
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Abstract Ischemia-reperfusion injury following surgery and transplantation can lead to irreversible multiorgan failure. Intracellular calcium overload is associated to cellular death during ischemiareperfusion. A recently discovered heparin fragment (HF), trisulfated disaccharide (TD), that acts on sodium-calcium exchanger (NCX) decreasing intracellular Ca2+ , showed effectiveness on protecting hepatocytes from ischemia-reperfusion injury [1], such as protection during cardiac arrhythmias [2]. HF of different molecular weights and origins have TD in their basic unit; however, calcium dynamics is heterogeneous due to differences in molecular weight and structural conformation [3,4]. We evaluated a new bovine HF (BHF001) of ~8000 kDa, presenting similarity to fragments of porcine and synthetic origin; however, without anticoagulation properties [5]. We designed a model to study the intracellular Ca2+ behavior with administration of BHF001 in cell culture and in vivo experiments to analyze its cellular and systemic protection in rats submitted to liver ischemia-reperfusion injury.
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