TY - JOUR
T1 - Ameliorative effects of supplemental folinic acid on Lamotrigine-induced fetal malformations in the mouse
AU - Abdulrazzaq, Y. M.
AU - Shafiullah, M.
AU - Kochyil, J.
AU - Padmanabhan, R.
AU - Bastaki, S. M.A.
N1 - Funding Information:
We are indebted to Sheikh Hamdan Award for Medical Sciences for providing funds for this work (Grant No. MRG13/2005). We are also grateful to the College of Medicine and Health Sciences, UAE University for making available the laboratory facilities and animals, without which this work would not be possible. There are no conflicts of interest with any of the authors.
Publisher Copyright:
© 2018, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2018/9/1
Y1 - 2018/9/1
N2 - Data from our previous work indicate that Lamotrigine (LTG) is teratogenic in the mouse. In the present study, we attempted to determine the possible protective effects of exogenous folate on LTG-induced fetal anomalies in TO mouse. Experiment I entailed administering 4 mg/kg of folinic acid (FA) and (25 mg/kg) of LTG intraperitoneally three times on gestation day (GD) 8 to a group of mice; other groups were a group that received similar volumes of saline, a group that received LTG and Saline, a group that received FA and saline. Experiment 2 involved administering groups of mice with daily 3 doses FA (or proportionate volume of saline) on GD 5 through 10 and either 3 doses of saline on GD8, or 3 doses of LTG on GD8. Maternal plasma concentrations of FA, vitamin B12 and homocysteine were determined an hour after the last injection from one-half of all animals. The other half were allowed to go to term (GD18) when they were euthanized and their fetuses were examined for visceral and skeletal malformations. A high incidence of resorption, abortion, embryolethality, congenital malformations, and intrauterine growth restriction (IUGR), was observed in the LTG-treated group. Folic acid and B12 levels were decreased and homocysteine concentration increased significantly in LTG groups. Mice receiving LTG with FA had normal levels of folate, Vitamin B12 and homocysteine levels, and the fetuses had fewer birth defects similar to the controls which were given saline only. Supplemental FA ameliorated to a great extent the LTG-induced embryonic resorption and malformations and restored the FA status.
AB - Data from our previous work indicate that Lamotrigine (LTG) is teratogenic in the mouse. In the present study, we attempted to determine the possible protective effects of exogenous folate on LTG-induced fetal anomalies in TO mouse. Experiment I entailed administering 4 mg/kg of folinic acid (FA) and (25 mg/kg) of LTG intraperitoneally three times on gestation day (GD) 8 to a group of mice; other groups were a group that received similar volumes of saline, a group that received LTG and Saline, a group that received FA and saline. Experiment 2 involved administering groups of mice with daily 3 doses FA (or proportionate volume of saline) on GD 5 through 10 and either 3 doses of saline on GD8, or 3 doses of LTG on GD8. Maternal plasma concentrations of FA, vitamin B12 and homocysteine were determined an hour after the last injection from one-half of all animals. The other half were allowed to go to term (GD18) when they were euthanized and their fetuses were examined for visceral and skeletal malformations. A high incidence of resorption, abortion, embryolethality, congenital malformations, and intrauterine growth restriction (IUGR), was observed in the LTG-treated group. Folic acid and B12 levels were decreased and homocysteine concentration increased significantly in LTG groups. Mice receiving LTG with FA had normal levels of folate, Vitamin B12 and homocysteine levels, and the fetuses had fewer birth defects similar to the controls which were given saline only. Supplemental FA ameliorated to a great extent the LTG-induced embryonic resorption and malformations and restored the FA status.
KW - Birth defects
KW - Folic acid
KW - Homocysteine
KW - LTG
KW - Vitamin B12
UR - http://www.scopus.com/inward/record.url?scp=85040863660&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85040863660&partnerID=8YFLogxK
U2 - 10.1007/s11010-018-3285-0
DO - 10.1007/s11010-018-3285-0
M3 - Article
C2 - 29363057
AN - SCOPUS:85040863660
SN - 0300-8177
VL - 446
SP - 185
EP - 197
JO - Molecular and Cellular Biochemistry
JF - Molecular and Cellular Biochemistry
IS - 1-2
ER -