title: Evidence against protective role of sex hormone estrogen in Cisplatin-induced nephrotoxicity in ovarectomized rat model.
abstract: BACKGROUND
  Cisplatin (CP) is an effective drug in cancer therapy to treat the solid tumors, but it is accompanied with nephrotoxicity. The protective effect of estrogen in cardiovascular diseases is well-documented; but its nephron-protective effect against CP-induced nephrotoxicity is not completely understood.
  
  
  METHODS
  Thirty ovarectomized Wistar rats were divided in to five groups. Groups 1-3 received different doses of estradiol valerate (0.5, 2.5 and 10 mg/kg/week) in sesame oil for 4 weeks, and at the end of week 3, a single dose of CP (7 mg/kg, intraperitoneal [IP]) was administrated. Group 4 (positive control) received the same regimen as group 1-3 without estradiol without vehicle. The negative control group (Group 5) received sesame oil during the study. The animals were sacrificed 1 week after CP injection for histopathological studies.
  
  
  RESULTS
  The serum level of blood urea nitrogen and creatinine, kidney tissue damage score (KTDS), kidney weight and percentage of body weight change in CP-treated groups significantly increased (P < 0.05), however, there were no significant differences detected between the estrogen-treated groups (Groups 1-3) and the positive control group (Group 4). Although, estradiol administration enhanced the serum level of nitrite, it was not affected by CP. Finally, significant correlation between KTDS and kidney weight was detected (r (2) = 0.63, P < 0.01).
  
  
  CONCLUSIONS
  Estrogen is not nephron-protective against CP-induced nephrotoxicity. Moreover, it seems that the mechanism may be related to estrogen-induced oxidative stress in the kidney, which may promote the nephrotoxicity.
authors.affiliation: Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran ; Department of Basic Sciences Isfahan University of Payam Noor, Isfahan, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Pezeshki
authors.forename: Mehdi
authors.initials: M
authors.lastname: Nematbakhsh
authors.forename: Hamid
authors.initials: H
authors.lastname: Nasri
authors.forename: Ardeshir
authors.initials: A
authors.lastname: Talebi
authors.forename: Ali-Asghar
authors.initials: AA
authors.lastname: Pilehvarian
authors.forename: Tahereh
authors.initials: T
authors.lastname: Safari
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Eshraghi-Jazi
authors.forename: Maryam
authors.initials: M
authors.lastname: Haghighi
authors.forename: Farzaneh
authors.initials: F
authors.lastname: Ashrafi
keywords: Cisplatin; estrogen; nephrotoxicity; ovarectomized rat