title: The lung endothelin system: a potent therapeutic target with bosentan for the amelioration of lung alterations in a rat model of diabetes mellitus.
abstract: OBJECTIVE
  The aim of this study is to show the effect of a new mechanism on endothelin (ET) receptors in the physiopathology of diabetes-related pulmonary injury. We tested the hypothesis that dual ET-1 receptor antagonism via bosentan can reverse diabetes-induced lung injury.
  
  
  METHODS
  The rats (24 male) were separated into four groups: group 1 (HEALTHY): Control group; group 2 (DM): Streptozotocin 60 mg/kg (i.p.); group 3 (DM + BOS-1): Diabetes + bosentan 50 mg/kg per-os; group 4 (DM + BOS-2): Diabetes + bosentan 100 mg/kg per-os. The bosentan treatment was initiated immediately after the onset of STZ-induced diabetes and continued for 6 weeks.
  
  
  RESULTS
  In the treatment group, SOD activity was significantly increased, although GSH and MDA levels and TNF-α and TGF-β gene expression were decreased. Bosentan 50 mg/kg and bosentan 100 mg/kg showed a significantly down-regulatory effect on ET-1, ET-A, and ET-B mRNA expression.
  
  
  CONCLUSIONS
  In conclusion, increased endothelin levels in the lung associated with diabetes may be one cause of endothelial dysfunction, cytokine increase, and oxidant/antioxidant imbalance in the pathogenesis of complications that may develop during diabetes. With its multiple effects, bosentan therapy may be an effective option against complications that may develop in association with diabetes.
authors.affiliation: Department of Pediatric Endocrinology, Erzurum Regional Education and Research Hospital, 25100, Erzurum, Turkey, dratillacayir@gmail.com.
authors.forename: A
authors.initials: A
authors.lastname: Cayir
authors.forename: R A
authors.initials: RA
authors.lastname: Ugan
authors.forename: A
authors.initials: A
authors.lastname: Albayrak
authors.forename: D
authors.initials: D
authors.lastname: Kose
authors.forename: E
authors.initials: E
authors.lastname: Akpinar
authors.forename: Y
authors.initials: Y
authors.lastname: Cayir
authors.forename: H T
authors.initials: HT
authors.lastname: Atmaca
authors.forename: Z
authors.initials: Z
authors.lastname: Bayraktutan
authors.forename: M
authors.initials: M
authors.lastname: Kara
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D000818:Animals; D000077300:Bosentan; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism; D065128:Endothelin Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D065128:Endothelin Receptor Antagonists; D013449:Sulfonamides; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D005978:Glutathione; D000077300:Bosentan
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