Prenatal exposure to an antiepileptic combination (levetiracetam and valproic acid) throughout gestation and postnatal sensorimotor development in mice
2023
Tip dokumenta:
Konferencijski prilog (Objavljena verzija)
,
© 2023 by the RAD Centre, Niš, Serbia
Metapodaci
Prikaz svih podataka o dokumentuApstrakt:
Introduction: Treatment of epilepsy always has an individual and unique path. Despite effective
classical and novel antiepileptic drugs (AEDs), monotherapy is limited and insufficient in some cases, such as
refractory epilepsy. Pregnant women with epilepsy are a population that requires a special approach. Protocol
guidelines and experience dictate the rational use of AEDs during pregnancy, which means that monotherapy
and the lowest therapeutic (curable) dose should be used. Epilepsy as a multifactorial condition involving
different categories of epileptic disorders sometimes requires treatment with highly potent therapeutic drugs,
such as valproic acid (VPA), which is known to be teratogenic. In some cases, not only can it not be
substituted, but it must also be combined with another drug. The combination of VPA and levetiracetam
(LEV), at a dosage of 1:1, achieves additive efficacy with no evidence of toxicity.
Aim: Thus, the aim of the present study was to investigate the sensorimotor development of mice whose
mothers were treated with a combination of VPA and LEV (1:1 ratio) during breeding and gestation.
Method: Adult, 8-week-old female NMRI mice were used in this study. Two groups of animals were
formed: one group (8 females) treated with a combination of LEV at a dose of 211 mg/kg/day (LEV-211) and
VPA at a dose of 200 mg/kg/day (VPA-200), and a control group (8 females) receiving an equivalent amount
of saline. The doses administered correspond to human doses of 1000 mg/day for both antiepileptic drugs.
All animals were treated subcutaneously into the loose skin on the back of the neck twice daily. Treatment
was initiated at the mating of males and females and continued throughout the entire period of breeding and
gestation. After the females gave birth, each of them was housed separately with her litter. Offspring were
separated by sex on postnatal day (PND) 21. Sensorimotor system performance and conditional learning
were assessed on PND25 and PND32 in the hot plate test (HPT).
Results: Female and male offspring treated prenatally with a combination of AEDs (LEV-211 + VPA 200) showed a significantly faster response than the control group on PND32, whereas female offspring also
showed a faster response than the control group on the first day of testing, PND25.
Conclusion: Considering the results of the HPT and the different sensorimotor responses in offspring
prenatally treated with antiepileptic drug combinations in animal models, it would be necessary for the
human practice to continuously monitor (until the end of adolescence) the children prenatally exposed to this
antiepileptic drug therapy.
Finansiranje / projekti:
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200007 (Univerzitet u Beogradu, Institut za biološka istraživanja 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
U:
- Ristić GS, editor. Book of Abstracts: Eleventh International Conference on Radiation, Natural Sciences, Medicine, Engineering, Technology and Ecology: RAD 2023; 2023 Jun 19-23; Herceg Novi, Montenegro. Niš, Serbia: RAD Centre; 2023. p. 29.
DOI: 10.21175/rad.abstr.book.2023.6.8
Cobiss ID: 121386249