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Drug Res (Stuttg) 2015; 65(05): 272-280
DOI: 10.1055/s-0034-1377024
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Endothelin Receptor Inhibition with Bosentan Delays Onset of Liver Injury in Streptozotocin-Induced Diabetic Condition

E. Demirci
1   Department of Pathology, Ataturk University, Faculty of Medicine, Erzurum, Turkey
,
I. Ferah
2   Department of Pharmacology, Ataturk University, Faculty of Pharmacy, Erzurum, Turkey
,
C. Gundogdu
1   Department of Pathology, Ataturk University, Faculty of Medicine, Erzurum, Turkey
,
S. Ozkanlar
3   Department of Biochemistry, Ataturk University, Faculty of Veterinary Medicine, Erzurum, Turkey
,
N. K. Baygutalp
4   Department of Pharmacy Management, Ataturk University, Faculty of Pharmacy, Erzurum, Turkey
,
Y. Bayir
5   Department of Biochemistry, Ataturk University, Faculty of Pharmacy, Erzurum, Turkey
,
M. Calik
1   Department of Pathology, Ataturk University, Faculty of Medicine, Erzurum, Turkey
,
G. Ayaz
6   Department of Pharmacology, Ataturk University, Faculty of Medicine, Erzurum, Turkey
› Author Affiliations
Further Information

Publication History

received 28 March 2014

accepted 14 May 2014

Publication Date:
11 June 2014 (online)

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Abstract

Background: This study was designed to investigate the protective effects of bosentan an orally active non-peptide mixed ETA/ETB receptor antagonist, on liver injury in streptozotocin-induced diabetic rats.

Methods: 24 Albino-Wistar rats were randomly divided into 4 groups: healthy (Group 1), diabetic (Group 2) (60 mg/kg of streptozotocin i.p.), diabetic treated with bosentan 50 mg/kg (Group 3) and diabetic treated with bosentan 100 mg/kg (Group 4). The treatment of bosentan was initiated after streptozocin injection and continued for 60 days.

Results: Liver from diabetic rats showed significant increase in malondialdehyde (MDA) level and significant decrease in glutathione (GSH), and superoxide dismutase (SOD) activity. Endothelin (ET-1), tumor necrosis factor (TNF-α) and transforming growth factor beta (TGF-β) gene expression significantly increased in the diabetic groups in the rat liver tissue. Bosentan treatment showed a significant up-regulatory effect on ET-1, TNF-α and TGF-β mRNA expression. Results from histopathological evaluation of the liver were in accordance with our biochemical and molecular results.

Conclusions: These data provide clear evidence that bosentan treatment is associated with promising hepatoprotective effect against diabetes-induced liver damage via reduction of cell inflammation and oxidative damage. These data suggest that ET receptors may be an important actor in diabetes-related liver damage, and blockage of these receptors may become a target for preventing diabetic complications in the future.

Key words

diabetes - liver - endothelin - cytokines - oxidative stress - rat
 

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