The optimal dose of Adriamycin to create a viable rat model potentially applicable to congenital obstructive uropathy.

摘要

PURPOSE: 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.