Lesions and repair of cells of maternal mice after valproic acid (VPA) treatment on day 8 of pregnancy: an enzyme histochemical analysis

Abstract

Mice received a single teratogenic dose of the antiepileptic drug valproic acid (VPA; 500 mg/kg i.p.) on 8th d of pregnancy. The effects of VPA were studied primarily by enzyme histochemical means over a period of 48 h. Plasma membrane-associated hydrolases were more affected than lysosome-associated ones. Lesions were not found in the spleen, but a slight response, without morphological damages, was observed in the lung and thymus. Comparatively more severe injuries, which were not accompanied by clear-cut structural changes either, occurred in the liver. The most severe damages including morphological lesions were noticed especially in the proximal tubules of the kidney. The first damages were already seen after 3 h and concerned primarily the liver. After 12 h, a maximal response to VPA was detected in all organs. Repair of most of the enzymatic lesions set in after 24 h. After 48 h, lesions were not longer seen in the lung and thymus. In contrast, enzymatically and morphologically injured proximal renal tubules could still be found after this period as a response to a single dose of VPA; in the liver only enzymatic lesions were present at this stage.