Objectives: To evaluate impact of prenatal exposure to 5 fluorouracil (5 FU) on morphology, skeleton and viscera of rats and to evaluate the effect of folic acid (FA) supplementation on these changes.
Materials & Methods: The study included 30 pregnant female rats divided equally into three groups: Control group, (5 FU) group injected intravenously by (5 FU) 15 µgm/gm body weight (BW)/day and (5 FU) +FA group injected intravenously by (5 FU) 15 µgm/gm BW/day and received FA 100 ug/gm/day orally. Drug therapy was given daily from the 6th to 9th days of gestation. On the 20th day of gestation, all female rats were delivered by labarotomy. The uterus with the two ovaries were removed and examined for the number of corpora lutea of pregnancy and the number of implantation and resorption sites in each uterine horn. Crown rump length, head length and biparietal diameter were measured and BW was recorded. Apparent external gross abnormalities were detected. Alizarine red stained skeletons were studied for counting the number of ribs and vertebrae and examination for any skeletal abnormalities. Skeletal specimens were examined for scoring of ossification as being complete, delayed or absent. Hematoxylin and eosin stained skeletal sections were examined.
Results: (5 FU) induced reduction of number of corpra lutea and live fetuses compared to both control and (5 FU) + FA groups. All body measurements were smaller compared to control group with larger measurements in (5 FU) +FA group. BW was significantly lower in study groups compared to control group with significantly higher BW in (5 FU) +FA group. External examination of (5 FU) -treated rats showed large blood clots indicating late post-implantation resorption, macerated fetuses indicating prenatal fetal death and a large abdominal hematoma. Alizarine red stain showed evident failure of ossification of limb bones and incomplete ossification of skull bones, vertebrae and ribs are seen in (5FU) group. In (5FU) +FA group, folic acid partly improved most of the skeletal changes. Histological sections showed malformed mandible and hypertrophied nasal septum, bilaterally dilated lateral and third ventricles and malformed spinal cord and vertebrae.
Conclusion: Prenatal exposure to (5FU) induces manifest teratogenic effects especially altering the growth levels with multiple skeletal abnormalities. Additionally, (5FU) induced significant brain and spinal cord detrimental effects. FA supplementation could ameliorate (5FU)-induced changes but could not be a grantee for safe pregnancy outcome.
Keywords: 5 fluorouracil, prenatal exposure, Folic acid supplementation
|
