ESPE Abstracts (2014) 82 P-D-3-1-707

ESPE2014 Poster Category 3 Diabetes (13 abstracts)

The Lung Endothelin System: a Potent Therapeutic Target with Bosentan for the Amelioration of Lung Alterations in a Rat Model of Diabetes Mellitus

Atilla Cayir a , Zekai Halici b , Erol Akpinar b , Zafer Bayraktutan c & Mustafa Kara d


aDepartment of Pediatric Endocrinology, Regional Training and Research Hospital, Erzurum, Turkey; bDepartment of Pharmacology, Faculty of Medicine, Ataturk University, Erzurum, Turkey; cDepartment of Biochemistry, Regional Education and Research Hospital, Erzurum, Turkey; dDepartment of Pediatrics, Faculty of Medicine, Ataturk University, Erzurum, Turkey


Background: Endothelial dysfunction underlies lung and other organ complications developing in associated with diabetes. Endothelial dysfunction leads to an increase in cytokine levels and oxidative stress. Studies have shown that the endothelin plays significant roles in the development of diabetic complications.

Objective and hypotheses: The aim of this study is to show the effect of a new mechanism on endothelin receptors in the physiopathology of diabetes-related pulmonary injury.

Methods: The rats were separated into four groups: group 1 (SHAM): control group; group 2 (DM): streptozotocin 60 mg/kg (i.p.); group 3 (DM+BOS-1): streptozotocin 60 mg/kg (i.p.)+bosentan 50 mg/kg peros; group 4 (DM+BOS-2): streptozotocin 60 mg/kg (i.p.)+bosentan 100 mg/kg peros. The bosentan treatment was initiated immediately after occurred STZ induced diabetes and continued for 6 weeks.

Results: In the treatment group, SOD activity was significantly increased, although GSH and MDA levels and TNFα and TGFβ gene expression were decreased. BOS-1 and BOS-2 showed a significantly down-regulatory effect on ET-1, ET-A, and ET-B mRNA expression.

Conclusion: Following bosentan therapy, improvement in endothelial dysfunction, histopathological marked, and a decrease in cytokine levels were recorded, and the antioxidant balance progressed.

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