MORPHOLOGICAL AND MORPHOMETRIC ALTERATIONS INDUCED BY VALPROIC ACID ON RAT FETUSES' MECKEL'S CARTILAGE, LINGUAL MUSCULATURE, AND SUBMANDIBULAR GLAND
Author
Siéssere,Selma
Semprini,Marisa
Lopes,Ruberval A
Sala,Miguel A
Mattos,Maria G. C
Abstract
Valproic acid, an antiepileptic drug, is a well-known teratogenic agent; its main target organ is the neural tube, though organ malformations have also been described. The aim of the present work was to analyze the effects of valproic acid on embryo/fetal oral structures: Meckel's cartilage, muscles of the tongue, and submandibular gland. Rats received a intraperitoneal injected of Valproic acid (300mg/Kg) on the 10th day of their gestation. Females were sacrificed on day 20 post coitus, and fetuses were examined. No gross malformations were observed. The following morphological alterations were observed: lower body and placental weight; shorter umbilical cord length; submandibular gland parenchyma less differentiated with larger cellular cord and terminal buds, and increased nuclear volume; lingual muscles fibers disorganized and of smaller size, and smaller nuclear volume; rudimentary Meckel's cartilage with small chondrocytes and more abundant matrix. These data suggest that alterations in oral tissue, induced by valproic acid, result from a direct effect of the drug on tissues causing a delayed differentiation