title: The optimal dose of Adriamycin to create a viable rat model potentially applicable to congenital obstructive uropathy.
abstract: OBJECTIVE
  The Adriamycin rat model is an established model for different organ anomalies including congenital obstructive uropathy. In the current study, we carried out a dose-response analysis to find out the optimal dose of Adriamycin to create a viable rat model of obstructive uropathy.
  
  
  METHODS
  Thirty time-mated Sprague-Dawley rats were divided into 5 groups including 1 control group and 4 different treatment groups. The 4 Adriamycin dosage regimens investigated in this study were 1.25, 1.5, 1.75, and 2 mg/(kg d). Experimental rats (n = 24) were injected intraperitoneally with different doses of Adriamycin on gestational days 7 to 9 (6 rats in each group). Control rats (n = 6) were injected with an equivalent volume of saline on the same days. Viable term fetuses were harvested on gestational day 21 by cesarean delivery and dissected under a dissecting microscope. Serial transverse sections from urinary tract system were obtained for histological examination.
  
  
  RESULTS
  One hundred thirty-three viable fetuses were recovered from Adriamycin-treated rats, and 50 were from rats in the control group. There were no resorptions in the control group; however, 52 resorptions were recorded in Adriamycin groups. The rates of hydronephrosis and resorptions were 60% and 0%, 80.5% and 5.8%, 100% and 17.3%, and 100% and 76.9% at doses of 1.25, 1.50, 1.75, and 2 mg/(kg d), respectively. Histologic examination of the kidneys in the treated groups showed a significant decrease in renal parenchyma compared with the control group.
  
  
  CONCLUSIONS
  The dosage of 1.5 mg/(kg d) of Adriamycin yielded the highest number of viable hydronephrotic fetuses. At this dose, urinary abnormalities are milder; but the highest number of viable fetuses is provided, which is necessary to create a reproducible and viable animal model.
authors.affiliation: Department of Urology, Paediatric Urology Research Center, Children's Hospital Medical Center, Tehran University of Medical Sciences, Tehran 1998714616, Iran. kajbafzd@sina.tums.ac.ir
authors.forename: Abdol Mohammad
authors.initials: AM
authors.lastname: Kajbafzadeh
authors.forename: Niloufar
authors.initials: N
authors.lastname: Javan-Farazmand
authors.forename: Akram
authors.initials: A
authors.lastname: Motamedi
authors.forename: Maryam
authors.initials: M
authors.lastname: Monajemzadeh
authors.forename: Erfan
authors.initials: E
authors.lastname: Amini
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin; D005260:Female; D005327:Fetal Resorption / Q000139:chemically induced; D006869:Hydronephrosis / Q000209:etiology; D007668:Kidney / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014517:Ureteral Obstruction / Q000139:chemically induced / Q000150:complications / Q000151:congenital* / Q000473:pathology
chemical_list: D004317:Doxorubicin