title: Trisulfate Disaccharide Decreases Calcium Overload and Protects Liver Injury Secondary to Liver Ischemia/Reperfusion.
abstract: BACKGROUND
  Ischemia and reperfusion (I/R) causes tissue damage and intracellular calcium levels are a factor of cell death. Sodium calcium exchanger (NCX) regulates calcium extrusion and Trisulfated Disaccharide (TD) acts on NCX decreasing intracellular calcium through the inhibition of the exchange inhibitory peptide (XIP).
  
  
  OBJECTIVE
  The aims of this research are to evaluate TD effects in liver injury secondary to I/R in animals and in vitro action on cytosolic calcium of hepatocytes cultures under calcium overload.
  
  
  METHODS
  Wistar rats submitted to partial liver ischemia were divided in groups:
  
  
  METHODS
  (n = 10): surgical manipulation with no liver ischemia; Saline: (n = 15): rats receiving IV saline before reperfusion; and TD: (n = 15): rats receiving IV TD before reperfusion. Four hours after reperfusion, serum levels of AST, ALT, TNF-α, IL-6, and IL-10 were measured. Liver tissue samples were collected for mitochondrial function and malondialdehyde (MDA) content. Pulmonary vascular permeability and histologic parameters of liver were determined. TD effect on cytosolic calcium was evaluated in BRL3A hepatic rat cell cultures stimulated by thapsigargin pre and after treatment with TD.
  
  
  RESULTS
  AST, ALT, cytokines, liver MDA, mitochondrial dysfunction and hepatic histologic injury scores were less in TD group when compared to Saline Group (p<0.05) with no differences in pulmonary vascular permeability. In culture cells, TD diminished the intracellular calcium raise and prevented the calcium increase pre and after treatment with thapsigargin, respectively.
  
  
  CONCLUSIONS
  TD decreases liver cell damage, preserves mitochondrial function and increases hepatic tolerance to I/R injury by calcium extrusion in Ca2+ overload situations.
authors.affiliation: Department of Gastroenterology (LIM 37), Medical School, University of Sao Paulo (USP), Sao Paulo, Brazil.
authors.forename: Enio Rodrigues
authors.initials: ER
authors.lastname: Vasques
authors.affiliation: Department of Gastroenterology (LIM 37), Medical School, University of Sao Paulo (USP), Sao Paulo, Brazil.
authors.forename: Jose Eduardo Monteiro
authors.initials: JE
authors.lastname: Cunha
authors.affiliation: Department of Gastroenterology (LIM 37), Medical School, University of Sao Paulo (USP), Sao Paulo, Brazil.
authors.forename: Ana Maria Mendonca
authors.initials: AM
authors.lastname: Coelho
authors.affiliation: Department of Gastroenterology (LIM 37), Medical School, University of Sao Paulo (USP), Sao Paulo, Brazil.
authors.forename: Sandra N
authors.initials: SN
authors.lastname: Sampietre
authors.affiliation: Department of Gastroenterology (LIM 37), Medical School, University of Sao Paulo (USP), Sao Paulo, Brazil.
authors.forename: Rosely Antunes
authors.initials: RA
authors.lastname: Patzina
authors.affiliation: Department of Gastroenterology (LIM 37), Medical School, University of Sao Paulo (USP), Sao Paulo, Brazil.
authors.forename: Emilio Elias
authors.initials: EE
authors.lastname: Abdo
authors.affiliation: Department of Biochemistry, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Helena B
authors.initials: HB
authors.lastname: Nader
authors.affiliation: Department of Biochemistry, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Ivarne L S
authors.initials: IL
authors.lastname: Tersariol
authors.affiliation: Department of Biochemistry, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Marcelo Andrade
authors.initials: MA
authors.lastname: Lima
authors.affiliation: Department of Science and Technology, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Carlos M G
authors.initials: CM
authors.lastname: Godoy
authors.affiliation: Center of Natural and Human Sciences, Federal University of ABC, Sao Paulo, Brazil.
authors.forename: Tiago
authors.initials: T
authors.lastname: Rodrigues
authors.affiliation: Department of Gastroenterology (LIM 37), Medical School, University of Sao Paulo (USP), Sao Paulo, Brazil.
authors.forename: Eleazar
authors.initials: E
authors.lastname: Chaib
authors.affiliation: Department of Gastroenterology (LIM 37), Medical School, University of Sao Paulo (USP), Sao Paulo, Brazil.
authors.forename: Luiz A C
authors.initials: LA
authors.lastname: D'Albuquerque
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002199:Capillary Permeability; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D022781:Hepatocytes / Q000378:metabolism; D018836:Inflammation Mediators / Q000097:blood; D008107:Liver Diseases / Q000378:metabolism* / Q000473:pathology; D008111:Liver Function Tests; D008168:Lung / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism; D010084:Oxidation-Reduction; D010766:Phosphorylation; D051381:Rats; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D019831:Sodium-Calcium Exchanger / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D019831:Sodium-Calcium Exchanger; D008315:Malondialdehyde; D002118:Calcium