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

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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.

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.

Author information

Authors and Affiliations

  1. Department of Pediatric Endocrinology, Erzurum Regional Education and Research Hospital, 25100, Erzurum, Turkey

    A. Cayir

  2. Department of Pharmacology, Faculty of Medicine, Ataturk University, Erzurum, Turkey

    R. A. Ugan, A. Albayrak, D. Kose & E. Akpinar

  3. Department of Family Medicine, Faculty of Medicine, Ataturk University, Erzurum, Turkey

    Y. Cayir

  4. Department of Pathology, Faculty of Veterinary, Kirikkale University, Kirikkale, Turkey

    H. T. Atmaca

  5. Department of Biochemistry, Erzurum Regional Education and Research Hospital, Erzurum, Turkey

    Z. Bayraktutan

  6. Department of Pediatry, Faculty of Medicine, Ataturk University, Erzurum, Turkey

    M. Kara

Authors
  1. A. Cayir
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  2. R. A. Ugan
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  3. A. Albayrak
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  4. D. Kose
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  5. E. Akpinar
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  6. Y. Cayir
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  7. H. T. Atmaca
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  8. Z. Bayraktutan
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  9. M. Kara
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Corresponding author

Correspondence to A. Cayir.

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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

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