title: Administration of vitamin E and losartan as prophylaxes in cisplatin-induced nephrotoxicity model in rats.
abstract: BACKGROUND
  Cisplatin (cis-diamminedichloroplatinum II; CDDP) is used widely as an antitumor drug in clinics, but is accompanied with renal toxicity. The present study was designed to compare the effect of losartan and vitamin E as prophylaxes against CDDP-induced nephrotoxicity.
  
  
  METHODS
  Thirty-two Wistar rats were divided into 5 groups: group 1 receiving losartan 10 mg/kg; group 2, vitamin E in almond oil 1 g/kg; group 3, combination of group 1 and 2 regimens; group 4, almond oil; and group 5, negative control group. All groups were treated for a 4-day period, but at day 3, groups 1-4 received a single dose (6 mg/kg) of CDDP. The animals were sacrificed 1 week after CDDP administration.
  
  
  RESULTS
  Animals' weight did not change significantly, but increasing blood urea nitrogen and malondialdehyde levels were observed statistically in all CDDP-treated animals. No detectable change was observed in nitrite level, but serum osmolality in groups 1, 2 and 4 was different from that for group 5 (p<0.05). Kidney damage scoring showed no significant difference between group 2 and the negative control group (group 2: 1.0 ± 0.24; group 5: 0.40 ± 0.10; p>0.05) but a statistically significant difference from the positive control group (p<0.05). The tubular damage score of group 1 also was not statistically significantly different from that of the negative control group.
  
  
  CONCLUSIONS
  Although vitamin E or losartan as prophylaxes demonstrated some protective effects, the combination of losartan and vitamin E did not protect against CDDP-induced nephrotoxicity, for unknown reasons which may relate to pharmacokinetic or pharmacodynamic drug interactions.
authors.affiliation: Kidney Basic Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. nematbakhsh@med.mui.ac.ir
authors.forename: Mehdi
authors.initials: M
authors.lastname: Nematbakhsh
authors.forename: Farzaneh
authors.initials: F
authors.lastname: Ashrafi
authors.forename: Tahereh
authors.initials: T
authors.lastname: Safari
authors.forename: Ardeshir
authors.initials: A
authors.lastname: Talebi
authors.forename: Hamid
authors.initials: H
authors.lastname: Nasri
authors.forename: Mojgan
authors.initials: M
authors.lastname: Mortazavi
authors.forename: Mehdi
authors.initials: M
authors.lastname: Khazaei
authors.forename: Mohammad-Mehdi
authors.initials: MM
authors.lastname: Baradaran-Mahdavi
mesh_terms: D000818:Animals; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D002945:Cisplatin; D003404:Creatinine / Q000097:blood; D019610:Cytoprotection; D004195:Disease Models, Animal; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control* / Q000652:urine; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D009573:Nitrites / Q000097:blood / Q000652:urine; D009994:Osmolar Concentration; D020011:Protective Agents / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D014810:Vitamin E / Q000008:administration & dosage*
chemical_list: D009573:Nitrites; D020011:Protective Agents; D014810:Vitamin E; D008315:Malondialdehyde; D003404:Creatinine; D019808:Losartan; D002945:Cisplatin