Transplacental genotoxicity of antiepileptic drugs: animal model and pilot study on mother/newborn cohort.
Antiepileptic drugs (AED) as transplacental agents are known to have adverse effects on fetal development. Genotoxicity of AEDs is still not fully understood. The aim of present study was to investigate the transplacental genotoxicity of valproate on animal model and in 21 mothers and their newborns receiving AED. In both studies, in vivo micronucleus (MN) assay was used. Pregnant dams were exposed to Na-valproate (100mg/kg) on gestational days 12-14. Dams and pups receiving Na-valproate showed a significantly increased MN frequency (5.17 ± 1.17/1000; 5.20 ± 1.48/1000) compared to the control (1.0 ± 0.58/1000; 1.67 ± 1.03/1000). In mother/newborn study a significant increase of MN frequency was detected in newborns of mothers taking AEDs (3.09 ± 0.49/10,000) compared to the referent newborns (1.56 ± 0.22/10,000). The results of this study suggest that AEDs may act as transplacental genotoxins. Launching the mother/newborn cohorts for genotoxicological monitoring may give a significant new insight in health effects of AEDs.
Institute for Medical Research and Occupational Health, Zagreb, Croatia. afucic@imi.hr
Aleksandra
A
Fucic
Ranko
R
Stojković
Snježana
S
Miškov
Davor
D
Zeljezic
Darko
D
Markovic
Romana
R
Gjergja
Jelena
J
Katic
Ana Marija
AM
Jazbec
Tomislav Ivicevic
TI
Bakulic
Vida
V
Demarin
D000328:Adult; D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000009:adverse effects* / Q000633:toxicity*; D015331:Cohort Studies; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015162:Micronucleus Tests; D009153:Mutagens / Q000009:adverse effects* / Q000633:toxicity*; D010865:Pilot Projects; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000188:drug therapy*; D011297:Prenatal Exposure Delayed Effects / Q000097:blood*; D012156:Reticulocytes / Q000187:drug effects; D014635:Valproic Acid / Q000009:adverse effects / Q000633:toxicity; D055815:Young Adult
D000927:Anticonvulsants; D009153:Mutagens; D014635:Valproic Acid