title: Role of endothelin-1 antagonist; bosentan, against cisplatin-induced nephrotoxicity in male and female rats.
abstract: BACKGROUND
  Cisplatin (CP) is a chemotherapy drug, with the major side effect of nephrotoxicity. The level of endothelin-1 (ET-1) increases during nephrotoxicity, which is accompanied with vasoconstrictive properties. Bosentan (BOS) is a nonselective ET-1 receptor antagonist, having vasodilatory and anti-hypertension effects. The purpose of this study was to investigate the renoprotective effect of BOS against CP-induced nephrotoxicity in male and female rats.
  
  
  METHODS
  Male and female rats were divided into six groups; groups 1-3 and 4-6 were male and female rats, respectively. Animals in groups 1 and 4 were considered as negative control and groups 2 and 5 considered as positive control groups received BOS (30 mg/kg/day) alone and CP (2.5 mg/kg/day) alone, respectively, for 1-week. The animals in groups 3 and 6 were treated with both CP and BOS. Finally, serum parameters were measured, and the kidney tissue was subjected to staining to evaluate tissue damage.
  
  
  RESULTS
  The serum levels of blood urea nitrogen and creatinine, kidney tissue damage score and kidney weight elevated, and body weight significantly decreased in both CP alone and in CP plus BOS-treated groups when compared with the control groups (P < 0.05), while BOS did not ameliorate these parameters neither in males nor in females. No significant differences were observed in serum levels of nitrite and malondialdehyde between the groups, but kidney tissue level of nitrite decreased significantly in CP alone and CP plus BOS-treated groups (P < 0.05).
  
  
  CONCLUSIONS
  Renoprotective effect of BOS, as ET-1 blocker, was not observed against CP-induced nephrotoxicity neither in male nor in female rats. This is while BOS promoted the severity of injuries in females.
authors.affiliation: Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran ; Department of Physiology, Islamic Azad University, Jahrom Brunch, Jahrom, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Jokar
authors.affiliation: Department of Physiology, Islamic Azad University, Jahrom Brunch, Jahrom, Iran ; Department of Physiology, Isfahan University of Medical Sciences, Isfahan, Iran ; Isfahan MN Institute of Basic and Applied Sciences Research, Isfahan, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Nematbakhsh
authors.affiliation: Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Moeini
authors.affiliation: Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Ardeshir
authors.initials: A
authors.lastname: Talebi
keywords: Bosentan; cisplatin; gender; nephrotoxicity; rat