Effects of pre- and postnatal cysteamine exposure on renal function in the rat.
The safety of cysteamine after renal transplantation and during pregnancy is an important issue, since girls with cystinosis are in better health on cysteamine therapy and thus more likely to become pregnant. In the first study, cysteamine was given to pregnant rats on days 6.5-18.5 post conception in oral doses of 0, 37.5, 75, 100, and 150 mg/kg per day. The dams were sacrificed on day 20.5, the fetal kidneys removed and prepared for histological examination. In the second study, cysteamine was given to dams on days 6.5-19.5 post conception in oral doses of 0, 37.5, 50, and 75 mg/kg per day. Dams were allowed to give birth naturally and pups were given cysteamine on days 4-21 to yield the same oral doses of cysteamine given to the dam. Renal function was evaluated on day 35. Histological examination of fetal kidneys revealed no changes even in kidneys from fetuses with growth retardation and malformations. Furthermore, there were no alterations in renal function in offspring on day 35. These findings demonstrate that cysteamine therapy does not affect renal development in the rat. Further investigations will be required to prove whether cysteamine therapy has the potential to affect renal development in the human.
Assadi
F K
FK
Division of Nephrology, Department of Pediatrics, Alfred I. duPont Hospital for Children and Thomas Jefferson University, P.O. Box 269, Wilmington, DE 19899-0269, USA. fassadi@nemours.org
McCue
P
P
Jefferis
S
S
Shi
M
M
Beckman
D A
DA
D000818:Animals; D003539:Cystaphos / Q000008:administration & dosage* / Q000633:toxicity; D003543:Cysteamine / Q000008:administration & dosage / Q000633:toxicity*; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D006868:Hydrolysis; D007668:Kidney / Q000187:drug effects* / Q000196:embryology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013723:Teratogens / Q000633:toxicity
D013723:Teratogens; D003543:Cysteamine; D003539:Cystaphos