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Effects of perinatal diazepam exposure on the liver of rats
L H Tan1, T Mariam, S Shahryar
1Institute of Anatomy, Heinrich Heine University, Düsseldorf, Germany.
Diazepam is routinely used in obstetrics in the treatment of maternal eclampsia or as anesthetic induction during deliveries or cesarean sections. We investigated here the effects of perinatal diazepam treatment on the liver of Sprague Dawley rats. From 15th day of gestation to birth 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 third (DZ3) with 10 mg DZ/kg b.w. After birth respective treatment was continued 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 120th day and then sacrificed. After fixation in formaldehyde serial paraffin sections were processed with proliferating cell nuclear antigen (PCNA), autofluorescence of lipofuscin and Elastica v. Gieson staining. Livers from 12 day old rats showed increased levels of PCNA marked hepatocytes and lipofuscin containing cells. Livers from 120 day old animals exhibited increased levels of PCNA cells especially with weakly stained nuclei, the number of lipofuscin containing cells were decreased in DZ1 and DZ2 but reached in DZ3 the similar number as control. Statistical analysis showed that quantification of Kupffer cells lacked significance. To conclude livers of 12 day old animals demonstrated a stimulated DNA synthesis and an accumulation of nondegradable residues. Livers from 120 day old rats demonstrated an increase in number of potentially proliferating hepatocytes by increased levels of weakly stained PCNA nuclei. At lower dosage DZ seems to inhibit lipofuscinogenesis, at highest dosage DZ accumulates non-degradable residues. Elastica v. Gieson staining was not suitable to quantify Kupffer cells with certainty.
Diazepam is routinely used in obstetrics in the treatment of maternal eclampsia or as anesthetic induction during deliveries or cesarean sections. We investigated here the effects of perinatal diazepam treatment on the liver of Sprague Dawley rats. From 15th day of gestation to birth 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 third (DZ3) with 10 mg DZ/kg b.w. After birth respective treatment was continued 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 120th day and then sacrificed. After fixation in formaldehyde serial paraffin sections were processed with proliferating cell nuclear antigen (PCNA), autofluorescence of lipofuscin and Elastica v. Gieson staining. Livers from 12 day old rats showed increased levels of PCNA marked hepatocytes and lipofuscin containing cells. Livers from 120 day old animals exhibited increased levels of PCNA cells especially with weakly stained nuclei, the number of lipofuscin containing cells were decreased in DZ1 and DZ2 but reached in DZ3 the similar number as control. Statistical analysis showed that quantification of Kupffer cells lacked significance. To conclude livers of 12 day old animals demonstrated a stimulated DNA synthesis and an accumulation of nondegradable residues. Livers from 120 day old rats demonstrated an increase in number of potentially proliferating hepatocytes by increased levels of weakly stained PCNA nuclei. At lower dosage DZ seems to inhibit lipofuscinogenesis, at highest dosage DZ accumulates non-degradable residues. Elastica v. Gieson staining was not suitable to quantify Kupffer cells with certainty.
