The teratogenic effect of cyclophosphamide on the embryos of albino rats and the protective effect of folic acid: morphologic study

Abstract

Background: Folic acid can protect tissues against the side effects of cytotoxic drugs by removing free radicals and prevention of oxidative damage. Material and Methods: 28 adult pregnant female albino rats were divided into groups as follows: Group I: (control group) 12 rats were further subdivided into two equal subgroups: Subgroup Ia: (negative control group) received saline. Subgroup Ib: (positive control group) received folic acid (2.4mg/kg/day). Group II: (experimental group) 10 rats received Cyclophosphamide (CP) (15 mg/kg) single intraperitoneal injection on the 9th day of gestation. Group III: (protected group) 6 rats received folic acid (2.4 mg/kg/day) and Cyclophosphamide (15mg/kg). The treatments except CP were given by orogastric tube from 1st to 19th GD. The skeletons were double stained by Alizarin red and Alcian blue stains and examined by Olympus SZ dissecting stereomicroscope.Results: Various eye, ear, tongue, and fusion defects were recorded. Skeletal anomalies were in the form of incomplete and un-ossified skull bones, open arch of atlas, incomplete ossification of sacral vertebrae, supernumerary sacral vertebra, rib, and incomplete ossification and wavy ribs, incomplete ossification of sternum, and metacarpus, metatarsus and phalanges. Their incidence increased significantly in the experimental group compared to the control group while it decreased significantly in the protected group for all reported anomalies except for incomplete ossification of skull bones and vertebrae and supernumerary sacral vertebrae and ribs.Conclusion: Cyclophosphamide is a teratogenic drug and folic acid has a protective role against its teratogenicity.