| Object:This research aims to evaluate the maternal toxicity and embryo-fetal development toxicity and teratogenicity of female Sprague-Dawley rats after oral administration metacavir during their first6-15pregnant days, which provide a reference for clinical safety about the metacavi. Method:81rats mated successfully were randomly divided into four groups, the low dose group (n=20), the middle dose group (n=20), the high dose group (n=21) and the control group (n=20), respectively, the low dose group, the middle dose group and the high dose group were administered orally (o.r) with the metacavi liquor with the dose of50,100,200,mg/kg (effective dose in rats40,20,10times); the control group were administered orally with double distilled water. The rat were administered every days with the same dose for continuous ten days during the6-15days of pregnancy. Testing indicators and methods,1) The death condition and clinical toxicity appearance were observed twice every day during experimental stage.2) The body weight at the0,3,6,10,13,16and20pregnant days were recorded.3) the pregnancy rat were anatomied when pregnancy20days, the major organs weight and pregnant uterine of each animal were weight, the number of corpus luteum, mplantation, early and late (?) fetal, live births and stillbirths were counted.4) The live births were judged gender,(?) weighted body weight, were inspected malformations of the appearance and variability.5) Half of per litter fetal rat were obtained hand section to detect internal organs of malformations and variability, the other half received skeletal deformity and variability inspection.Result:During the experimental period, we observed each dose group had good appearance condition, acted normally on the whole, but7in the high dose group,5in the middle dose group shown decrease of feed intake and weight gain compared with control group. And there also shown the change of weight gain involved in the administration in the experiment. The correction value of weight gain in the first6-20pregnant days didn’t show significant difference in low dose group, but shown significant difference in middle dose group (p<0.05), and extreme significant diference in high dose group (p<0.01) compared with negative control group. Major organs weight, pregnant uterine weight, corpus luteum, the number of implantation, early and late absorption fetal, waterloo average number of live births of pregnant rats had no statistical significant diffrences between each metacavir dose group and control group, and pathology change concerned with administration can’t be seen. The number of stillbirths of high dose group shown significant difference compared with negative (p<0.05) control group, but the litter incidence had no significant difference. Average weight of live births of each metacavir dose group didn’t shown significant difference compared with negative control group (p>0.05). The gender difference, appearance and internal organs abnormity concered with administration also can’t be observed during the experiment. Skeletal survey indicated that skeleton of each fetal rat grow well.The present research concluded that metacavir will induce some maternal toxicity influences at its200mg/kg/day (effective dose in rats40times) to Sprague-Dawley rats. The embryo toxicity shown slightly weight loss individually,200mg/kg/day group had higher stillbirths rate than control group, but the litter incidence rate was low. Every dose groups’skeleton grow well, shown no teratogenic effect, metacavir had no adverse effects on fetal rat growth, which all together indicated that≤200mg/kg/day dose, metacavir would not induce teratogenic effect to Sprague-Dawley rats. |
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