Journal of Endocrinological Investigation

, Volume 38, Issue 9, pp 987–998 | Cite as

The lung endothelin system: a potent therapeutic target with bosentan for the amelioration of lung alterations in a rat model of diabetes mellitus

  • A. CayirEmail author
  • R. A. Ugan
  • A. Albayrak
  • D. Kose
  • E. Akpinar
  • Y. Cayir
  • H. T. Atmaca
  • Z. Bayraktutan
  • M. Kara
Original Article



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.


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.


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.


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.


Bosentan Lung injury Endothelin system Diabetes 



We would like to thank Marc Iglarz and Actelion Pharmaceuticals Ltd., for providing us bosentan.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standard

Animal experiments and procedures were performed in accordance with the national guidelines for the use and care of laboratory animals and were approved by Ataturk University’s local animal care committee.

Informed consent

All authors consent journal’s entire rule and confirm the publication of manuscript in the Journal of Endocrinological Investigation.


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Copyright information

© Italian Society of Endocrinology (SIE) 2015

Authors and Affiliations

  • A. Cayir
    • 1
    Email author
  • R. A. Ugan
    • 2
  • A. Albayrak
    • 2
  • D. Kose
    • 2
  • E. Akpinar
    • 2
  • Y. Cayir
    • 3
  • H. T. Atmaca
    • 4
  • Z. Bayraktutan
    • 5
  • M. Kara
    • 6
  1. 1.Department of Pediatric EndocrinologyErzurum Regional Education and Research HospitalErzurumTurkey
  2. 2.Department of Pharmacology, Faculty of MedicineAtaturk UniversityErzurumTurkey
  3. 3.Department of Family Medicine, Faculty of MedicineAtaturk UniversityErzurumTurkey
  4. 4.Department of Pathology, Faculty of VeterinaryKirikkale UniversityKirikkaleTurkey
  5. 5.Department of BiochemistryErzurum Regional Education and Research HospitalErzurumTurkey
  6. 6.Department of Pediatry, Faculty of MedicineAtaturk UniversityErzurumTurkey

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