Prenatal toxicity of Ascaris pepsin inhibitor in mice.
The developmental toxicity of pepsin inhibitor isolated from Ascaris suum, a gastrointestinal nematode parasite, was evaluated. An embryo-fetal development study was conducted in BALB/c mice. Groups of 21 mated females were treated by intraperitoneal injection (0.3 ml/30 g body weight) with 0.9% NaCl solution vehicle or isolated Ascaris pepsin inhibitor (API) at dose levels of 50, 100, 150 or 200mg/kg body weight/day on gestation days (GD) 6-15. Maternal food consumption, body weight, and clinical signs were monitored throughout gestation. Cesarean sections were performed on GD 18 and gravid uterine weight, implantation sites, early and late resorptions, live and dead fetuses were collected. Live fetuses were weighed and examined for external, visceral and skeletal variations and malformations. Maternal body weight gain, gravid uterine weight, food consumption were significantly decreased after injection of higher doses of API (100-200mg/kg/day). All doses of API exhibited an embryotoxic effect (high rate of intrauterine resorption). The percentage of postimplantation loss in the groups with administered API was higher (over 4-11 times) than that in control group. Fetotoxicity was observed in all treatment groups in a dose-related manner and it was evidenced by increased dead fetuses, decreased fetal weight, increased visceral variations and reduced skeletal ossification. Fetal hydronephrosis and internal hydrocephalus were noted at 150, and 200mg/kg/day. In summary, the maternal toxicity no-observed-adverse-effect level (NOAEL) was 50mg/kg/day and the low-observed-adverse-effect level (LOAEL) was 100mg/kg/day under the conditions of this study. However, the developmental toxicity LOAEL was 50mg/kg/day based on decreased fetal body weight and prenatal mortality.
Blaszkowska
Joanna
J
Department of Biology and Medical Parasitology, Biology and Medical Genetics, Medical University of Lodz, Pl. Hallera 1, 90-647 Lodz, Poland. biolparazyt@poczta.onet.pl
D000014:Abnormalities, Drug-Induced; D000818:Animals; D017165:Ascaris suum / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus / Q000187:drug effects*; D015801:Helminth Proteins / Q000633:toxicity*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019055:No-Observed-Adverse-Effect Level; D010434:Pepsin A / Q000037:antagonists & inhibitors*
D015801:Helminth Proteins; D010434:Pepsin A