title: The effect of an specific inducible NO synthase inhibitor, S-methylisothiourea hemisulfate on cisplatin-induced nephrotoxicity; gender-related differences.
abstract: BACKGROUND
  It has been previously demonstrated that the increase of nitric oxide (NO) level may promote cisplatin (CP)-induced nephrotoxicity. The aim of this study was to investigate the role of inducible NO synthase (iNOS) inhibitor to prevent CP-induced nephrotoxicity.
  
  
  METHODS
  Four groups of male and four groups of female rats were treated daily with vehicle, S-methylisothiourea hemisulfate (SMT) as a selective iNOS inhibitor (5 mg/kg/twice a day), CP (2.5 mg/kg/day), and CP + SMT for 6 days. Then, all animals were sacrificed and the serum levels of creatinine (Cr), blood urea nitrogen (BUN), nitrite, and malondialdehyde (MDA) were measured. The kidney was removed immediately for histopathological study.
  
  
  RESULTS
  Our results showed that inhibition of iNOS by SMT could make different response in male and female animals. SMT therapy in male animals decreased serum BUN, Cr, nitrite, and MDA levels; and it also protected kidney against CP-induced nephrotoxicity.
  
  
  CONCLUSIONS
  It is concluded that decrease in NO production by SMT has a beneficial effect on reducing CP-induced nephrotoxicity in male. However, such beneficial effect was not observed in female animals.
authors: Department of Physiology, Hormozgan University of Medical Sciences, Bandar Abbas, Isfahan, Iran ; Molecular Medicine Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Isfahan, Iran ; Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
authors: Mansooreh
authors: M
authors: Ghayyoomi
authors: Department of Physiology, Hormozgan University of Medical Sciences, Bandar Abbas, Isfahan, Iran ; Molecular Medicine Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Isfahan, Iran.
authors: Nepton
authors: N
authors: Soltani
authors: Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran ; Department of Physiology Isfahan University of Medical Sciences, Isfahan, Iran ; Isfahan MN Institute of Basic and Applied Sciences Research, Isfahan, Iran.
authors: Mehdi
authors: M
authors: Nematbakhsh
authors: Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
authors: Fatemeh
authors: F
authors: Moslemi
authors: Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran ; Department of Clinical Pathology, Isfahan University of Medical Sciences, Isfahan, Iran.
authors: Ardeshir
authors: A
authors: Talebi
authors: Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
authors: Soheila
authors: S
authors: Shirdavani
authors: Department of Physiology, Hormozgan University of Medical Sciences, Bandar Abbas, Isfahan, Iran.
authors: Farzaneh
authors: F
authors: Razmjoo
keywords: Cisplatin; SMT; nephrotoxicity; nitric oxide