title: Effect of enalapril in cisplatin-induced nephrotoxicity in rats; gender-related difference.
abstract: BACKGROUND
  The function of renin angiotensin system (RAS) is gender-related, and this system affects cisplatin (CP)-induced nephrotoxicity. In this study, we compared the effect of enalapril as an angiotensin-converting enzyme (ACE) inhibitor on CP-induced nephrotoxicity between male and female rats.
  
  
  METHODS
  Sixty-two adult male and female Wistar rats were divided into eight groups. Both genders received CP (2.5 mg/kg, i.p.) and enalapril (30 mg/kg, i.p.) for 7 days in compared with CP alone or enalapril alone or vehicle alone treated groups. At the end of the experiment, blood samples were obtained, and the kidney tissue was investigated for histopathological changes.
  
  
  RESULTS
  CP increased the serum levels of blood urea nitrogen and creatinine as well as kidney weight and kidney tissue damage score in both genders (P < 0.05). However, not only enalapril failed to ameliorate the aforementioned parameters in both genders, but also it intensified nephrotoxicity in females (P < 0.05). In addition, enalapril enhanced body weight loss induced by CP in females (P < 0.05). CP alone decreased kidney level of nitrite in both genders (P < 0.05) and enalapril could not reverse this decreasing. The combination of enalapril and CP significantly increased serum level of nitrite in females, but this was not observed in males (P < 0.05).
  
  
  CONCLUSIONS
  Enalapril as an ACE inhibitor failed to ameliorate nephrotoxicity induced by CP in both male and female rats. In addition, enalapril aggravated CP-induced nephrotoxicity in female possibly due to gender-dependent RAS response.
authors.affiliation: Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Zamani
authors.affiliation: Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran; Department of Physiology, Isfahan University of Medical Sciences, Isfahan, Iran; Isfahan 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: Fatemeh
authors.initials: F
authors.lastname: Eshraghi-Jazi
authors.affiliation: Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran; Department of Clinical Pathology, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Ardeshir
authors.initials: A
authors.lastname: Talebi
authors.affiliation: Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Sima
authors.initials: S
authors.lastname: Jilanchi
authors.affiliation: Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Mitra
authors.initials: M
authors.lastname: Navidi
authors.affiliation: Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Soheila
authors.initials: S
authors.lastname: Shirdavani
authors.affiliation: Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Farzaneh
authors.initials: F
authors.lastname: Ashrafi
keywords: Cisplatin; enalapril; gender; nephrotoxicity; rat