title: Endothelin receptor inhibition with bosentan delays onset of liver injury in streptozotocin-induced diabetic condition.
abstract: BACKGROUND
  This study was designed to investigate the protective effects of bosentan an orally active non-peptide mixed ETA/ETB receptor antagonist, on liver injury in streptozotocin-induced diabetic rats.
  
  
  METHODS
  24 Albino-Wistar rats were randomly divided into 4 groups: healthy (Group 1), diabetic (Group 2) (60 mg/kg of streptozotocin i.p.), diabetic treated with bosentan 50 mg/kg (Group 3) and diabetic treated with bosentan 100 mg/kg (Group 4). The treatment of bosentan was initiated after streptozocin injection and continued for 60 days.
  
  
  RESULTS
  Liver from diabetic rats showed significant increase in malondialdehyde (MDA) level and significant decrease in glutathione (GSH), and superoxide dismutase (SOD) activity. Endothelin (ET-1), tumor necrosis factor (TNF-α) and transforming growth factor beta (TGF-β) gene expression significantly increased in the diabetic groups in the rat liver tissue. Bosentan treatment showed a significant up-regulatory effect on ET-1, TNF-α and TGF-β mRNA expression. Results from histopathological evaluation of the liver were in accordance with our biochemical and molecular results.
  
  
  CONCLUSIONS
  These data provide clear evidence that bosentan treatment is associated with promising hepatoprotective effect against diabetes-induced liver damage via reduction of cell inflammation and oxidative damage. These data suggest that ET receptors may be an important actor in diabetes-related liver damage, and blockage of these receptors may become a target for preventing diabetic complications in the future.
authors.affiliation: Department of Pathology, Ataturk University, Faculty of Medicine, Erzurum, Turkey.
authors.forename: E
authors.initials: E
authors.lastname: Demirci
authors.affiliation: Department of Pharmacology, Ataturk University, Faculty of Pharmacy, Erzurum, Turkey.
authors.forename: I
authors.initials: I
authors.lastname: Ferah
authors.affiliation: Department of Pathology, Ataturk University, Faculty of Medicine, Erzurum, Turkey.
authors.forename: C
authors.initials: C
authors.lastname: Gundogdu
authors.affiliation: Department of Biochemistry, Ataturk University, Faculty of Veterinary Medicine, Erzurum, Turkey.
authors.forename: S
authors.initials: S
authors.lastname: Ozkanlar
authors.affiliation: Department of Pharmacy Management, Ataturk University, Faculty of Pharmacy, Erzurum, Turkey.
authors.forename: N K
authors.initials: NK
authors.lastname: Baygutalp
authors.affiliation: Department of Biochemistry, Ataturk University, Faculty of Pharmacy, Erzurum, Turkey.
authors.forename: Y
authors.initials: Y
authors.lastname: Bayir
authors.affiliation: Department of Pathology, Ataturk University, Faculty of Medicine, Erzurum, Turkey.
authors.forename: M
authors.initials: M
authors.lastname: Calik
authors.affiliation: Department of Pharmacology, Ataturk University, Faculty of Medicine, Erzurum, Turkey.
authors.forename: G
authors.initials: G
authors.lastname: Ayaz
mesh_terms: D000818:Animals; D000077300:Bosentan; D056486:Chemical and Drug Induced Liver Injury / Q000150:complications / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications*; D065128:Endothelin Receptor Antagonists / Q000494:pharmacology*; D019332:Endothelin-1 / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051381:Rats; D013311:Streptozocin; D013449:Sulfonamides / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D013449:Sulfonamides; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D013311:Streptozocin; D013482:Superoxide Dismutase; D005978:Glutathione; D000077300:Bosentan