الفهرس 
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Abstract
HCV infection is a worldwide health problem. Egypt is one of the highest prevalence in adults. The prevalence of infection in pregnancy is between 1% and 8%. Treatment during pregnancy has been associated with many problems. Unfortunately, till now there is no approval for an antiviral drug to be used in pregnancy. A new group of antiviral agents has emerged known as directing acting antivirals (DAAs). Daclatasvir (DCV) is one of the second generation DAAs that has pangenotypic activity.
Aim of the work: Was to explore the possible:
• Teratogenic effects of daclatasvir administration on fetuses of the pregnant mice.
• Histological effects of daclatasvir on the liver cells of the pregnant mice.
Materials and Methods: Forty adult pregnant female mice were divided into two main groups:
• group I (control group), included 10 mice which received distilled water.
• group II (DCV group): included 30 mice subdivided into three equal groups:
1. group IIa: received DCV 12.5 mg/kg/day
2. group IIb: received DCV 25 mg/kg/day
3. group IIc: received DCV 50 mg/kg/day
Females in each group are placed into the cages with males (two females/ one male per cage). The female mice were examined for the presence of vaginal plug on the next morning. The female mice proved to have vaginal plug, suspected to be pregnant, were isolated in separate cages (four/cage).
• They received the drug orally from GD6 to GD15. The pregnant mice were sacrificed (at GD 18-19) after taking blood samples for biochemical analysis. Liver specimens were processed for histological and morphometric analysis.
• Fetuses were weighted and examined for any external anomalies then; they were processed for skeletal examination.
The results of the present study could be summarized as follows:
• Maternal toxicity in the form of decrease in maternal body weight gain and increased maternal mortalities were observed in DCV treated groups.
• Fetal toxicity was observed in DCV treated groups, in a dose dependent manner, in the form of
1. Increased rate of fetal resorptions (early and late)
2. Decreased fetal body weight
3. A group of external anomalies were encountered in the form of; hyper-extension of forelimb, internal rotation of forelimb and hind limb and subcutaneous hemorrhages.
4. Skeletal abnormalities reported in the form of incomplete ossification of parts of the skeleton (skull, vertebral column, ribs, sternum, forelimbs, and hindlimb). There was a significant increase in number of fetuses depicted incomplete ossification in DCV treated groups as compared to the control.
• Common hepatocellular changes in the three experimental groups showing; disturbed hepatic architecture, hypereosinophilic foci with indistinct boundaries, nuclear alterations, cellular vacuolation and prominent Von-kupffer cells. The presence of basophilic foci was prominent in GIIc. Increased collagen deposition and high levels of liver enzymes were mostly prominent in GIIa more than GIIc and GIIb respectively. These findings were concomitant with fibrosis, cirrhosis and perneoplastic lesion in the liver in a dose dependent manner.
• Based on these findings, DCV showed a dose dependent maternal, fetal and hepatic toxic effect at doses 12.5, 25, and 50 mg/ kg /day in mice. Putting in consideration that the least dose used in the present study was equivalent to the average of the human recommended daily dose of DCV which is 60.9 mg /day.