title: Role of endothelin receptor antagonist; bosentan in cisplatin-induced nephrotoxicity in ovariectomized estradiol treated rats.
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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Water & Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Alieh
authors.initials: A
authors.lastname: Zahedi
authors.affiliation: Water & Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran ; Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran ; Isfahan MN Institute of Basic & Applied Sciences Research, Isfahan, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Nematbakhsh
authors.affiliation: Water & Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Moeini
authors.affiliation: Water & Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran ; Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Ardeshir
authors.initials: A
authors.lastname: Talebi
keywords: Bosentan; Cisplatin; Estradiol; Nephrotoxicity; Rat