The Effects of Valproic Acid on the Skeletal Development and the Ameliorative Effects of Combined Use of Folic Acid and Vitamin E in Pregnant Albino Rats

Gamal Abdel Salam; Omar ABd Alaziz Allam

doi:doi:10.11648/j.ijcda.20150103.13

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The Effects of Valproic Acid on the Skeletal Development and the Ameliorative Effects of Combined Use of Folic Acid and Vitamin E in Pregnant Albino Rats

Gamal Abdel Salam, Omar ABd Alaziz Allam

Published in International Journal of Clinical and Developmental Anatomy (Volume 1, Issue 3)

Received: 6 August 2015 Accepted: 13 August 2015 Published: 19 August 2015

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Abstract

Objectives: To evaluate skeletal developmental defects secondary to chronic valproic acid (VPA) use during pregnancy and the extent of ameliorative effect of combined use of vitamin E and folic acid (FA) during VPA therapy. Materials and Methods: Thirty virgin female albino rats were allowed to get pregnant and were divided into three equal groups: Control group received no medications; VPA group received oral VPA 400 mg/kg body weight (BW) starting on gestational day (GD) 1 till GD20 and Prophylaxis group received oral VPA (400 mg/kg BW) and vitamin E 250 mg/kg BW and folic acid 100 µg/kg BW using gastric tube starting on GD1 till GD20. At GD20, uterine horns were examined for resorption sites, alive or dead fetuses. Extracted living fetuses were examined for BW, crown-rump length (CRL), and antero-posterior (AP) and biparietal diameters and for congenital malformations. Results: VPA significantly reduced all body measurements of living dams compared to control dams. Prophylaxis therapy significantly increased BW, CRL and AP skull diameter compared to VPA dams. The GD20 fetus of VPA group showed delayed ossification of skull bones with wide anterior fontanel (AF) and widely separated parietal bones, very small ossification center (OC) for hyoid bone. Caudal vertebrae were unossified or showed very small OC with no evident OC for calcaneous, metatarsal bones or distal phalanges. Fetuses of prophylaxis group showed slightly wide AF than that of control animals and parietal bones are separated to lesser extent than VPA group. Mandible is developed, with an OC for hyoid bone and sternebrae are seen. Six caudal vertebrae and few OC in phalanges are seen, but no OC in calcaneous. Conclusion: VPA chronic administration during pregnancy showed deleterious effects on fetal body measurements and skeletal system development. Concomitant administration of vitamin E and FA significantly ameliorated these changes.

Published in	International Journal of Clinical and Developmental Anatomy (Volume 1, Issue 3)
DOI	10.11648/j.ijcda.20150103.13
Page(s)	70-78
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Valproic Acid, Folic Acid, Vitamin E, Pregnancy, Skeletal Defects

References

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Gamal Abdel Salam, Omar ABd Alaziz Allam. (2015). The Effects of Valproic Acid on the Skeletal Development and the Ameliorative Effects of Combined Use of Folic Acid and Vitamin E in Pregnant Albino Rats. International Journal of Clinical and Developmental Anatomy, 1(3), 70-78. https://doi.org/10.11648/j.ijcda.20150103.13

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ACS Style

Gamal Abdel Salam; Omar ABd Alaziz Allam. The Effects of Valproic Acid on the Skeletal Development and the Ameliorative Effects of Combined Use of Folic Acid and Vitamin E in Pregnant Albino Rats. Int. J. Clin. Dev. Anat. 2015, 1(3), 70-78. doi: 10.11648/j.ijcda.20150103.13

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AMA Style

Gamal Abdel Salam, Omar ABd Alaziz Allam. The Effects of Valproic Acid on the Skeletal Development and the Ameliorative Effects of Combined Use of Folic Acid and Vitamin E in Pregnant Albino Rats. Int J Clin Dev Anat. 2015;1(3):70-78. doi: 10.11648/j.ijcda.20150103.13

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@article{10.11648/j.ijcda.20150103.13,
  author = {Gamal Abdel Salam and Omar ABd Alaziz Allam},
  title = {The Effects of Valproic Acid on the Skeletal Development and the Ameliorative Effects of Combined Use of Folic Acid and Vitamin E in Pregnant Albino Rats},
  journal = {International Journal of Clinical and Developmental Anatomy},
  volume = {1},
  number = {3},
  pages = {70-78},
  doi = {10.11648/j.ijcda.20150103.13},
  url = {https://doi.org/10.11648/j.ijcda.20150103.13},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijcda.20150103.13},
  abstract = {Objectives: To evaluate skeletal developmental defects secondary to chronic valproic acid (VPA) use during pregnancy and the extent of ameliorative effect of combined use of vitamin E and folic acid (FA) during VPA therapy. Materials and Methods: Thirty virgin female albino rats were allowed to get pregnant and were divided into three equal groups: Control group received no medications; VPA group received oral VPA 400 mg/kg body weight (BW) starting on gestational day (GD) 1 till GD20 and Prophylaxis group received oral VPA (400 mg/kg BW) and vitamin E 250 mg/kg BW and folic acid 100 µg/kg BW using gastric tube starting on GD1 till GD20. At GD20, uterine horns were examined for resorption sites, alive or dead fetuses. Extracted living fetuses were examined for BW, crown-rump length (CRL), and antero-posterior (AP) and biparietal diameters and for congenital malformations. Results: VPA significantly reduced all body measurements of living dams compared to control dams. Prophylaxis therapy significantly increased BW, CRL and AP skull diameter compared to VPA dams. The GD20 fetus of VPA group showed delayed ossification of skull bones with wide anterior fontanel (AF) and widely separated parietal bones, very small ossification center (OC) for hyoid bone. Caudal vertebrae were unossified or showed very small OC with no evident OC for calcaneous, metatarsal bones or distal phalanges. Fetuses of prophylaxis group showed slightly wide AF than that of control animals and parietal bones are separated to lesser extent than VPA group. Mandible is developed, with an OC for hyoid bone and sternebrae are seen. Six caudal vertebrae and few OC in phalanges are seen, but no OC in calcaneous. Conclusion: VPA chronic administration during pregnancy showed deleterious effects on fetal body measurements and skeletal system development. Concomitant administration of vitamin E and FA significantly ameliorated these changes.},
 year = {2015}
}

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TY  - JOUR
T1  - The Effects of Valproic Acid on the Skeletal Development and the Ameliorative Effects of Combined Use of Folic Acid and Vitamin E in Pregnant Albino Rats
AU  - Gamal Abdel Salam
AU  - Omar ABd Alaziz Allam
Y1  - 2015/08/19
PY  - 2015
N1  - https://doi.org/10.11648/j.ijcda.20150103.13
DO  - 10.11648/j.ijcda.20150103.13
T2  - International Journal of Clinical and Developmental Anatomy
JF  - International Journal of Clinical and Developmental Anatomy
JO  - International Journal of Clinical and Developmental Anatomy
SP  - 70
EP  - 78
PB  - Science Publishing Group
SN  - 2469-8008
UR  - https://doi.org/10.11648/j.ijcda.20150103.13
AB  - Objectives: To evaluate skeletal developmental defects secondary to chronic valproic acid (VPA) use during pregnancy and the extent of ameliorative effect of combined use of vitamin E and folic acid (FA) during VPA therapy. Materials and Methods: Thirty virgin female albino rats were allowed to get pregnant and were divided into three equal groups: Control group received no medications; VPA group received oral VPA 400 mg/kg body weight (BW) starting on gestational day (GD) 1 till GD20 and Prophylaxis group received oral VPA (400 mg/kg BW) and vitamin E 250 mg/kg BW and folic acid 100 µg/kg BW using gastric tube starting on GD1 till GD20. At GD20, uterine horns were examined for resorption sites, alive or dead fetuses. Extracted living fetuses were examined for BW, crown-rump length (CRL), and antero-posterior (AP) and biparietal diameters and for congenital malformations. Results: VPA significantly reduced all body measurements of living dams compared to control dams. Prophylaxis therapy significantly increased BW, CRL and AP skull diameter compared to VPA dams. The GD20 fetus of VPA group showed delayed ossification of skull bones with wide anterior fontanel (AF) and widely separated parietal bones, very small ossification center (OC) for hyoid bone. Caudal vertebrae were unossified or showed very small OC with no evident OC for calcaneous, metatarsal bones or distal phalanges. Fetuses of prophylaxis group showed slightly wide AF than that of control animals and parietal bones are separated to lesser extent than VPA group. Mandible is developed, with an OC for hyoid bone and sternebrae are seen. Six caudal vertebrae and few OC in phalanges are seen, but no OC in calcaneous. Conclusion: VPA chronic administration during pregnancy showed deleterious effects on fetal body measurements and skeletal system development. Concomitant administration of vitamin E and FA significantly ameliorated these changes.
VL  - 1
IS  - 3
ER  -

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Author Information

Gamal Abdel Salam

Anatomy Department, Faculty of Medicine, Benha University, Benha City, Egypt
Omar ABd Alaziz Allam

Anatomy Department, Faculty of Medicine, Benha University, Benha City, Egypt

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Gamal Abdel Salam, Omar ABd Alaziz Allam. (2015). The Effects of Valproic Acid on the Skeletal Development and the Ameliorative Effects of Combined Use of Folic Acid and Vitamin E in Pregnant Albino Rats. International Journal of Clinical and Developmental Anatomy, 1(3), 70-78. https://doi.org/10.11648/j.ijcda.20150103.13

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ACS Style

Gamal Abdel Salam; Omar ABd Alaziz Allam. The Effects of Valproic Acid on the Skeletal Development and the Ameliorative Effects of Combined Use of Folic Acid and Vitamin E in Pregnant Albino Rats. Int. J. Clin. Dev. Anat. 2015, 1(3), 70-78. doi: 10.11648/j.ijcda.20150103.13

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AMA Style

Gamal Abdel Salam, Omar ABd Alaziz Allam. The Effects of Valproic Acid on the Skeletal Development and the Ameliorative Effects of Combined Use of Folic Acid and Vitamin E in Pregnant Albino Rats. Int J Clin Dev Anat. 2015;1(3):70-78. doi: 10.11648/j.ijcda.20150103.13

Copy | Download

@article{10.11648/j.ijcda.20150103.13,
  author = {Gamal Abdel Salam and Omar ABd Alaziz Allam},
  title = {The Effects of Valproic Acid on the Skeletal Development and the Ameliorative Effects of Combined Use of Folic Acid and Vitamin E in Pregnant Albino Rats},
  journal = {International Journal of Clinical and Developmental Anatomy},
  volume = {1},
  number = {3},
  pages = {70-78},
  doi = {10.11648/j.ijcda.20150103.13},
  url = {https://doi.org/10.11648/j.ijcda.20150103.13},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijcda.20150103.13},
  abstract = {Objectives: To evaluate skeletal developmental defects secondary to chronic valproic acid (VPA) use during pregnancy and the extent of ameliorative effect of combined use of vitamin E and folic acid (FA) during VPA therapy. Materials and Methods: Thirty virgin female albino rats were allowed to get pregnant and were divided into three equal groups: Control group received no medications; VPA group received oral VPA 400 mg/kg body weight (BW) starting on gestational day (GD) 1 till GD20 and Prophylaxis group received oral VPA (400 mg/kg BW) and vitamin E 250 mg/kg BW and folic acid 100 µg/kg BW using gastric tube starting on GD1 till GD20. At GD20, uterine horns were examined for resorption sites, alive or dead fetuses. Extracted living fetuses were examined for BW, crown-rump length (CRL), and antero-posterior (AP) and biparietal diameters and for congenital malformations. Results: VPA significantly reduced all body measurements of living dams compared to control dams. Prophylaxis therapy significantly increased BW, CRL and AP skull diameter compared to VPA dams. The GD20 fetus of VPA group showed delayed ossification of skull bones with wide anterior fontanel (AF) and widely separated parietal bones, very small ossification center (OC) for hyoid bone. Caudal vertebrae were unossified or showed very small OC with no evident OC for calcaneous, metatarsal bones or distal phalanges. Fetuses of prophylaxis group showed slightly wide AF than that of control animals and parietal bones are separated to lesser extent than VPA group. Mandible is developed, with an OC for hyoid bone and sternebrae are seen. Six caudal vertebrae and few OC in phalanges are seen, but no OC in calcaneous. Conclusion: VPA chronic administration during pregnancy showed deleterious effects on fetal body measurements and skeletal system development. Concomitant administration of vitamin E and FA significantly ameliorated these changes.},
 year = {2015}
}

Copy | Download

TY  - JOUR
T1  - The Effects of Valproic Acid on the Skeletal Development and the Ameliorative Effects of Combined Use of Folic Acid and Vitamin E in Pregnant Albino Rats
AU  - Gamal Abdel Salam
AU  - Omar ABd Alaziz Allam
Y1  - 2015/08/19
PY  - 2015
N1  - https://doi.org/10.11648/j.ijcda.20150103.13
DO  - 10.11648/j.ijcda.20150103.13
T2  - International Journal of Clinical and Developmental Anatomy
JF  - International Journal of Clinical and Developmental Anatomy
JO  - International Journal of Clinical and Developmental Anatomy
SP  - 70
EP  - 78
PB  - Science Publishing Group
SN  - 2469-8008
UR  - https://doi.org/10.11648/j.ijcda.20150103.13
AB  - Objectives: To evaluate skeletal developmental defects secondary to chronic valproic acid (VPA) use during pregnancy and the extent of ameliorative effect of combined use of vitamin E and folic acid (FA) during VPA therapy. Materials and Methods: Thirty virgin female albino rats were allowed to get pregnant and were divided into three equal groups: Control group received no medications; VPA group received oral VPA 400 mg/kg body weight (BW) starting on gestational day (GD) 1 till GD20 and Prophylaxis group received oral VPA (400 mg/kg BW) and vitamin E 250 mg/kg BW and folic acid 100 µg/kg BW using gastric tube starting on GD1 till GD20. At GD20, uterine horns were examined for resorption sites, alive or dead fetuses. Extracted living fetuses were examined for BW, crown-rump length (CRL), and antero-posterior (AP) and biparietal diameters and for congenital malformations. Results: VPA significantly reduced all body measurements of living dams compared to control dams. Prophylaxis therapy significantly increased BW, CRL and AP skull diameter compared to VPA dams. The GD20 fetus of VPA group showed delayed ossification of skull bones with wide anterior fontanel (AF) and widely separated parietal bones, very small ossification center (OC) for hyoid bone. Caudal vertebrae were unossified or showed very small OC with no evident OC for calcaneous, metatarsal bones or distal phalanges. Fetuses of prophylaxis group showed slightly wide AF than that of control animals and parietal bones are separated to lesser extent than VPA group. Mandible is developed, with an OC for hyoid bone and sternebrae are seen. Six caudal vertebrae and few OC in phalanges are seen, but no OC in calcaneous. Conclusion: VPA chronic administration during pregnancy showed deleterious effects on fetal body measurements and skeletal system development. Concomitant administration of vitamin E and FA significantly ameliorated these changes.
VL  - 1
IS  - 3
ER  -

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