TY  - JOUR
A1  - ,  
T1  - Valproate induced effects on development in the rat are partially prevented by folinic acid and S-adenosylmethionine
JO  - Eur. J. Anat.
SN  - 1136-4890
Y1  - 2000
VL  - 4
SP  - 23
EP  - 33
UR  - http://www.eurjanat.com/web/paper.php?id=00010023
KW  - folinic acid
KW  - s adenosylmethionine
KW  - valproic acid
KW  - animal experiment
KW  - animal model
KW  - animal tissue
KW  - article
KW  - congenital malformation
KW  - controlled study
KW  - dose response
KW  - drug effect
KW  - female
KW  - female fertility
KW  - fetus malformation
KW  - immunohistochemistry
KW  - Kupffer cell
KW  - liver injury
KW  - neural tube defect
KW  - nonhuman
KW  - pregnancy
KW  - rat
KW  - rat strain
KW  - T lymphocyte
KW  - teratogenesis
N2  - Valproic acid (VPA) is a teratogenic agent that induces a wide range of tissue alterations, including neural tube defects (NTD) and skull malformations. There is an established dose-dependent effect of VPA and types of malformations in rat. The aim of the present study was to determine morphological, histological and immunohistochemical alterations under an assumedly non teratogenic VPA exposure. Potential prevention by coadministration with folinic acid (FA) and S-adenosylmethionine (SAM) was also assessed. Wistar rats were treated during gestation with VPA (300 mg/kg/d on days 8, 9, and 10), either alone or in combination with FA (4 mg/kg/d on days 8, 9, and 10) or SAM (10 mg/kg/d from days 1 to 10). Rats were terminated on day 21, and implantation sites were counted. VPA induced a lower fertility rate due to a higher number of resorptions, which were reduced by coadministration of either FA or SAM. Foetal weight and length were unaffected by VPA treatment. Hepatic injury was observed in foetuses treated with VPA. Studies with specific antibodies against Kupffer cells and T-lymphocytes also showed that Kupffer cells appeared more frequently in the VPA+FA and VPA+SAM groups, whereas folinic acid and exogenous SAM were able to reverse the decrease in VPA-induced foetal liver T-lymphocyte cells. VPA treatment resulted in skeletal modifications in the skull, appendicular bones, vertebrae and ribs. Folate was able to prevent these defects, whereas SAM-coadministration did not show this protective action. The results are discussed on the basis that VPA may induce other potential alterations different from NTD whose long-term effects are not well understood at present.
ER  -