J Nephropathol. 2015;4(4):134-140.
doi: 10.12860/jnp.2015.25
PMID: 26457261
PMCID: PMC4596298
Scopus id: 84943634740
  Abstract View: 1682
  PDF Download: 774

Original Article

Role of endothelin receptor antagonist; bosentan in cisplatin-induced nephrotoxicity in ovariectomized estradiol treated rats

Alieh Zahedi 1, Mehdi Nematbakhsh 1,2,3 * , Maryam Moeini 1, Ardeshir Talebi 1,2

1 Water & Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
2 Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
3 Isfahan MN Institute of Basic & Applied Sciences Research, Isfahan, Iran
4 Department of Clinical Pathology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
*Corresponding author: Prof. Mehdi Nematbakhsh, Email: nematbakhsh@med.mui.ac.ir

Abstract

Background: Endothelin-1 (ET-1) is a vasoconstrictor peptide that mediates cell proliferation, fibrosis, and inflammation. ET-1 has 2 receptors A and B.

Objectives: The present study investigated whether administration of ET-1 receptor type A antagonist leads to protect cisplatin (CP) induced nephrotoxicity in ovariectomized-estradiol (Es) treated rats.

Materials and Methods: Thirty-six ovariectomized Wistar rats were divided into 6 groups. Group 1 received CP (2.5 mg/kg/day) for one week. Groups 2 and 3 received 2 different doses of Es (0.25 and 0.5 mg/kg/week) for 3 weeks, but CP was started in the third week. Group 4 was treated as group 1, but bosentan (BOS, 30 mg/kg/day) was also added. Groups 5 and 6 treated similar to groups 2 and 3 but CP and BOS were added in the third week. At the end of the experiment, blood samples were obtained, and the animals were sacrificed for histopathological investigation of kidney tissue.

Results: The serum levels of creatinine (Cr) and blood urea nitrogen (BUN) increased by CP; however, BOS significantly elevated the BUN and Cr levels that were increased by CP administration (P < 0.05). Co-treatment of Es, BOS, and CP decreased the serum levels of BUN, Cr, and malondialdehyde (MDA) when compared with the group treated with BOS plus CP (P < 0.05). Such finding was obtained for kidney tissue damage score (KTDS). As expected, Es significantly increased uterus weight (P < 0.05). The groups were not significantly different in terms of serum and kidney nitrite, kidney weight (KW), and bodyweight

Conclusions: According to our findings, BOS could not protect renal functions against CP-induced nephrotoxicity. In contrast, Es alone or accompanied with BOS could protect the kidney against CP-induced nephrotoxicity via reduction of BUN, Cr, and KTDS.

Implication for health policy/practice/research/medical education:

To find the role of endothelin receptor antagonist; bosentan (BOS) in cisplatin-induced nephrotoxicity in ovariectomized estradiol treated rats, we found, BOS could not protect renal functions against cisplatin-induced nephrotoxicity. In contrast, estradiol alone or accompanied with BOS could protect the kidney against cisplatin-induced nephrotoxicity by reduction of blood urea nitrogen (BUN), creatinine (Cr), and kidney tissue damage score.

Please cite this paper as: Zahedi A, Nematbakhsh M, Moeini M, Talebi A. Role of endothelin receptor antagonist; bosentan in cisplatin-induced nephrotoxicity in ovariectomized estradiol treated rats. J Nephropathol. 2015; 4(4):134-140. DOI: 10.12860/ jnp.2015.25

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First published online: 01 Oct 2015
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