EFFECTS OF PERINATAL DIAZEPAM EXPOSURE ON THE LIVER OF RATS

Diazepam is routinely used in obstetrics in the treatment of maternal eclampsia or as anesthetic induction during deliveries or cesarean sec tions. We investigated here the effects of perinatal diazepam treatmen t on the liver of Sprague Dawley rats. From 15th day of gestation to b irth pregnant rats were treated daily in the first experimental group (DZ1) with 2.5 mg DZ/kg b.w., s.c., the second (DZ2) with 5 and the th ird (DZ3) with 10 mg DZ/kg b.w. After birth respective treatment was c ontinued to the pups till 5th day postnatal. One half of pups from DZ2 and control was sacrificed at 12th day, the other were raised to 120t h day and then sacrificed. After fixation in formaldehyde serial paraf fin sections were processed with proliferating cell nuclear antigen (P CNA), autofluorescence of lipofuscin and Elastica v. Gieson staining. Livers from 12 day old rats showed increased levels of PCNA marked hep atocytes and lipofuscin containing cells. Livers from 120 day old anim als exhibited increased levels of PCNA cells especially with weakly st ained nuclei, the number of lipofuscin containing cells were decreased in DZ1 and DZ2 but reached in DZ3 the similar number as control. Stat istical analysis showed that quantification of Kupffer cells lacked si gnificance. To conclude livers of 12 day old animals demonstrated a st imulated DNA synthesis and an accumulation of nondegradable residues. Livers from 120 day old rats demonstrated an increase in number of pot entially proliferating hepatocytes by increased levels of weakly stain ed PCNA nuclei. At lower dosage DZ seems to inhibit lipofuscino-genesi s, at highest dosage DZ accumulates non-degradable residues. Elastica v. Gieson staining was not suitable to quantify Kupffer cells with cer tainty.