Effect of lithium on rat embryos in culture: growth, development, compartmental distribution and lack of a protective effect of inositol.
Lithium chloride (LiCl) was tested at various concentrations (50, 100, 150 and 200 micrograms/ml) using a rat whole-embryo culture system beginning on gestation day 9.5 (headfold stage) in order to establish a concentration-response relationship. Open neural tubes--as described in former publications (Tesh 1988)--were not induced by lithium. A significant reduction of embryonic growth and development occurred at the lowest concentration tested (50 micrograms/ml). Clear-cut dysmorphogenetic effects (absence of the eye cup, kink in the spinal anlage, "bleb" at the rostral head region) occurred at a concentration of 150 micrograms/ml LiCl. LiCl concentrations in the embryo, visceral yolk sac, exocoelomic fluid and medium were determined after the embryos had been cultured for 48 h in the presence of a moderately embryotoxic dose of LiCl (3.5 mEq/l or 150 micrograms/ml). Medium supplementation with myo-inositol in different concentrations was ineffective in antagonizing the embryotoxicity induced by LiCl.
Klug
S
S
Institut für Toxikologie und Embryopharmakologie, Freie Universität Berlin, Federal Republic of Germany.
Collins
M
M
Nagao
T
T
Merker
H J
HJ
Neubert
D
D
D000818:Animals; D001825:Body Fluid Compartments; D002712:Chlorides / Q000493:pharmacokinetics / Q000633:toxicity*; D003470:Culture Media; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D007294:Inositol / Q000494:pharmacology*; D007700:Kinetics; D008094:Lithium / Q000493:pharmacokinetics / Q000633:toxicity*; D018021:Lithium Chloride; D008297:Male; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar
D002712:Chlorides; D003470:Culture Media; D007294:Inositol; D008094:Lithium; D018021:Lithium Chloride