Mutagenic and Teratogenic Effects of Indomethacin and Cyclosporine-A on Dams and Fetuses of Mice.

Abstract

Eighty pregnant female mice were alloted among 16 groups. The animals were given intraperitoneal injection equalized to the therapeutic doses used for human. Indomethacin was given (25, 75 mg/kg b.wt.) and cyclosporine-A was given (5, 10, 15 mg/kg b.wt.). They induced significant increase in fetal resorption and significant decrease in fetal body weight. Also, reduction in the sizes of the skeletons of embryos was observed. Dosage of 150 mg/kg b.wt. of indomethacin was the lethal dose to dams. Various chromosomal aberrations in maternal bone marrow cells and embryos cells and mitotic activity were recorded, quantitated and statistically analyzed. Indomethacin (75 mg/kg) induced more chromosomal aberrations in both pregnant females as well as fetuses than the lower dose (25 mg/kg). Cyclosporine-A (15 mg/kg b.wt.) induced an increase in chromosomal aberrations in bone marrow cells of female mice than lower dose (5, 10 mg/kg b.wt.), while no significant differences were observed between the (5, 10 mg/kg) doses. Also, cyclosporine-A (15 mg/kg) showed highly significant increase in chromosomal aberrations in embryos than medium (10 mg/kg) or lower doses (5 mg/kg).