Teratogenicity ofN-(4-hydroxyphenyl) -all-trans-retinamide in rats and rabbits

Autor: John H. Krayer, Kenel Mf, Merz Ea, Pritchard Jf
Rok vydání: 1988
Předmět:
Zdroj: Teratogenesis, Carcinogenesis, and Mutagenesis. 8:1-11
ISSN: 1520-6866
0270-3211
DOI: 10.1002/tcm.1770080102
Popis: N-(4-hydroxyphenyl)-all-trans-retinamide (HPR) has potential efficacy in the treatment of dermatologic, arthritic, and neoplastic disorders. The teratogenicity of such a compound is of special concern in light of the known adverse effects of retinoids, in general, on the developing conceptus. In these studies, Sprague-Dawley rats and New Zealand White rabbits were treated orally from gestation days 6 to 15 and 6 to 18, respectively, with 0, 20, 125, or 800 mg/kg/day of HPR. In rat fetuses, low incidences of hydrocephaly (mid- and high-dosage groups) were observed. Fetal tissue (ng/g) and maternal plasma (ng/ml) concentrations of HPR, its major metabolite (N-[4-methoxyphenyl] retinamide [MPR]) and retinol were determined in separate groups of similarly-treated rats 3 h following the last dose on gestation day 15. Fetal tissue concentrations of HPR and MPR were approximately one-half maternal plasma concentrations. A dose related reduction in maternal plasma and fetal tissue concentrations of retinol were also observed. In mid- and high-dosage rabbit fetuses, a dose-related increase in the incidence of dome-shaped head was observed. Subsequent skeletal evaluation revealed delays in skull bone ossification and a widening of the frontal and frontoparietal sutures. Microphthalmia was also observed in two high-dosage fetuses. A dose-dependent and statistically significant reduction in maternal plasma retinol levels was observed across all dosage groups.
Databáze: OpenAIRE
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