Abstract
Purpose
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.
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Acknowledgments
We would like to thank Marc Iglarz and Actelion Pharmaceuticals Ltd., for providing us bosentan.
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The authors declare that they have no conflict of interest.
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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.
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Cayir, A., Ugan, R.A., Albayrak, A. et al. The lung endothelin system: a potent therapeutic target with bosentan for the amelioration of lung alterations in a rat model of diabetes mellitus. J Endocrinol Invest 38, 987–998 (2015). https://doi.org/10.1007/s40618-015-0282-y
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DOI: https://doi.org/10.1007/s40618-015-0282-y