alpha-chymotrypsin and Abnormalities--Drug-Induced

Administration intraperitoneally of the Ascaris alpha-chymotrypsin inhibitor (40-300 mg/kg/day) at a late stage of organogenesis (8-12 days of gestation) disturbed course of mouse pregnancy. The low doses of alpha-chymotrypsin inhibitor (40-80 mg/kg/day) significantly decreased the number of live fetuses per litter, increased the number of fetal resorptions. The symptoms of maternal toxicity that occurred after administration of the highest doses of the inhibitor (80-300 mg/kg/day) to pregnant mice included: decreased body weight gain as compared to control, vaginal hemorrhage, intrauterine resorption of litters, abortions, altered behaviour of animals immediately after injection and death. There is a linear interrelationship between the logarithm of the doses of the inhibitor and mortality of pregnant mice. The DL50 value of the inhibitor for female was 116 mg/kg/day (confidence interval: 95.5-140.0 mg/kg/day).

Topics: Abnormalities, Drug-Induced; Animals; Ascaris; Body Weight; Chymotrypsin; Dose-Response Relationship, Drug; Female; Fetal Death; Fetal Resorption; Helminth Proteins; Maternal-Fetal Exchange; Mice; Mice, Inbred BALB C; Organ Size; Pregnancy; Pregnancy Complications, Parasitic; Pregnancy Outcome; Pregnancy, Animal; Teratogens

During investigations of biological activity of proteolysis inhibitors from Ascaris lumbricoides, teratogenic action of alfa-chymotrypsin inhibitor (ICH) was evaluated. The inhibitor was obtained by a method of Roli and Pudles and was applied parenterally at 8-12 day of pregnancy to BALB/c mice in doses of 20-80 mg/kg of mice per 24 hours. Control groups received respectively 1 cm3 of 0.9% NaCl or 80 mg of bovine albumin. Normal status of development of internal organs in 19-days old fetuses was evaluated by a method of Wilson and Dyban and of their skeletons according to Dawson. It was found that character and exacerbation of prenatal disturbances of mice development is conditioned by the ICH dose. Teratogenic action of ICH was apparent in fetuses after application to mice of 60 and 80 mg. Most frequent developmental defects were: cleft palate, brain hernia, fusion of ribs and curvature of spine. No defects were noted in control groups. Lower doses of ICH exhibited only embryotoxic effect.

Topics: Abnormalities, Drug-Induced; Animals; Ascariasis; Ascaris lumbricoides; Biological Factors; Chymotrypsin; Embryo, Mammalian; Embryo, Nonmammalian; Embryonic and Fetal Development; Female; Mice; Mice, Inbred BALB C; Pregnancy; Teratogens