Cyclosporine-induced fetotoxicity in the rat.
Female Lewis rats mated with DA male rats were given 25 or 10 mg/kg/day cyclosporine (CsA) from the time of mating to 20 days postcoitus when autopsies were performed. At the higher dose, characteristic drug-induced pathological changes in the mother were accompanied by a striking fetotoxic effect, resulting in a high incidence of fetal mortality or in runting. In addition, fetal kidneys that could be examined showed evidence of CsA-induced proximal tubular cell damage. These abnormalities were not found at the lower dosage of CsA. The fetotoxicity observed at 25 mg/kg did not appear to be dependent on major histocompatibility differences between parental strains, since it was also observed, at the same dosage, in syngeneically mated female Lewis rats.
D000818:Animals; D001663:Bilirubin / Q000097:blood; D003524:Cyclosporins / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000187:drug effects*; D007687:Kidney Tubules, Proximal / Q000473:pathology; D008431:Maternal-Fetal Exchange / Q000187:drug effects; D009336:Necrosis; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D051381:Rats; D011917:Rats, Inbred Lew
D003524:Cyclosporins; D001663:Bilirubin