Bone development in offspring of pregnant rats treated with carbamazepine: Evaluation by three different methods

GÜLER H., Esen E. E., BALCIOĞLU E., GÖKTEPE Ö., Yılmaz H., YAY A. H., ...More

Epilepsia, vol.63, no.12, pp.3066-3077, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 63 Issue: 12
  • Publication Date: 2022
  • Doi Number: 10.1111/epi.17422
  • Journal Name: Epilepsia
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.3066-3077
  • Keywords: bone development, carbamazepine, immunohistochemistry staining, pregnancy, scanning electron microscopy, ANTIEPILEPTIC DRUGS, MAJOR MALFORMATIONS, PRENATAL EXPOSURE, VALPROIC ACID, VITAMIN-D, EPILEPSY, CHILDREN, INFANTS, METABOLISM, TURNOVER
  • Kayseri University Affiliated: No


© 2022 International League Against Epilepsy.Objective: This study was carried out to determine the effect of intrauterine carbamazepine (CBZ) exposure on fetal bone development during pregnancy. Methods: In the study, 24 female Wistar pregnant rats were used. Rats were 20 weeks old. They had an average body weight of 150–200 g. Pregnant rats were randomly selected and divided (n = 6) into a control group, low-dose CBZ (10 mg/kg/day) group, medium-dose CBZ (25 mg/kg/day) group, and high-dose CBZ (50 mg/kg/day) group. The ossification length (mm) and ossification area (mm2) of the long bones of the fetuses in the experimental and control groups were calculated. The densities of alkaline phosphatase (AP) and tartrate-resistant acid phosphatase (TRAP) were analyzed. The ossification regions of the femurs of the fetuses were examined under a light microscope. Microstructural images of the femurs were evaluated with scanning electron microscope photographs. The densities of minerals involved in the ossification process were analyzed. Results: According to the results of the study, all three doses of CBZ caused loss of ossification areas, and it was observed that this bone loss also increased statistically significantly depending on the dose increase (p <.05). Calcium concentration decreased in the CBZ groups. When the electron microscope images were examined, it was determined that the cartilage matrix of the CBZ groups was thinned. In the histological evaluation of the groups, narrowing of the primary bone collar and smaller bone spicules in the ossification region compared to the control group were noted due to the increase in dose in the CBZ groups. In immunohistochemical staining, it was observed that the TRAP and AP expression values of the femurs were the lowest in the CBZ groups. These decreases were also statistically significant when compared with the control group. Significance: It was revealed with both microscopic and macroscopic findings that exposure to intrauterine CBZ negatively affected ossification and bone growth.