Investigation of the teratogenic potential of VLA-4 antagonist derivatives in rats.
Reprod Toxicol
; 49: 162-70, 2014 Nov.
Article
en En
| MEDLINE
| ID: mdl-25194688
ABSTRACT
Very late antigen-4 (VLA-4), which is concerned with cell-cell adhesion, plays important roles in development of the heart, and some VLA-4 antagonists cause cardiac anomalies. In this study, we evaluated the teratogenic potential of VLA-4 antagonist derivatives as screening, and investigated the conditions that induce cardiac anomalies. Seventeen compounds were orally administered to pregnant rats throughout the organogenesis period, and fetal examinations were performed. In addition, drug concentrations in the embryos were assayed. As a result, the incidence of ventricular septal defect (VSD) ranged from 0 to 100% depending on the compound. Plasma drug concentrations in the dams were related to increased incidence of VSD; however, these incidences were not increased when the concentration of the compound in the embryos at 24h after dosing was low. It is considered that continuous pharmacological activity in the embryo for more than 24h might disrupt closure of the ventricular septum.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Teratógenos
/
Integrina alfa4beta1
/
Defectos del Tabique Interventricular
Límite:
Animals
/
Pregnancy
Idioma:
En
Revista:
Reprod Toxicol
Asunto de la revista:
EMBRIOLOGIA
/
MEDICINA REPRODUTIVA
/
TOXICOLOGIA
Año:
2014
Tipo del documento:
Article