Effects of ascorbic acid on the mouse embryo and on cyclophosphamide-induced cephalic DNA strand breaks in vivo

Abstract

Pregnant C3H mice were exposed to 3.34 and 6.68 g ascorbic acid/kg body weight on the 11th day post-copulation, and to co-administration of a teratogenic dose of cyclophosphamide (CP, 15 mg/kg body weight). The effects on embryonal cephalic DNA strand breaks were assessed 16 h after drug administration. In order to establish whether vitamin C was embryotoxic or altered CP-induced toxicity, mice were sacrificed on day 18 after copulation to record fetal weights, gross morphological abnormalities, and fetal mortality. Administration of 3.34 g ascorbate/kg was not associated with demonstrable toxic effects but with 6.68 g ascorbic acid/kg there was a 46% incidence of fetal mortality. In embryos exposed to CP, 15 mg/kg, there was a decrease in fetal weight (median fetal weight 678 mg compared with 967 mg in controls), all fetuses were morphologically abnormal and 59% of cephalic DNA was double stranded compared with 81% for controls (p less than 0.001). When vitamin C, 3.34 g/kg, was co-administered with CP the incidence of DNA strand breaks remained unchanged. However, all fetuses were morphologically normal and there was no reduction in fetal weight. These findings demonstrate that administration of 6.68 g vitamin C/kg is toxic to the mouse embryo, but a lower dose of 3.34 g/kg is not, and has a protective effect against the toxic manifestations of CP. This protection is not associated with prevention of cephalic DNA strand breaks.

Effect of Drakshavaleha in cyclophosphamide induced weight loss and reduction in crown-rump length in developing mice embryo

“…Teratogenic doses of CP on day 11 after copulation is associated with a dose-related increase in embryo lethality, gross morphological abnormality and cephalic Deoxyribonucleic acid DNA strand breaks and a reduction in fetal weight DNA is the primary target of embryo-toxic mechanism of CP. [9]…”

Final Report of the Safety Assessment of L-Ascorbic Acid, Calcium Ascorbate, Magnesium Ascorbate, Magnesium Ascorbyl Phosphate, Sodium Ascorbate, and Sodium Ascorbyl Phosphate as Used in Cosmetics1

“…All fetuses treated with Ascorbic Acid and CP were morphologically normal and there was no reduction in fetal weight. These findings demonstrate that the administration of 6.68 g/kg Ascorbic Acid was toxic to the mouse embryo, but the lower dose was not and had a protective effect against the toxic manifestations of CP (Pillans et al 1990). Colomina et al (1994) dosed three groups of pregnant Swiss mice daily with aluminum hydroxide, Ascorbic Acid (85 mg/kg), or aluminum hydroxide (300 mg/kg) concurrent with Ascorbic 82 COSMETIC INGREDIENT REVIEW Acid (85 mg/kg) on gestational days 6 to 15 by gavage.…”

“…In a study by Pillans et al (1990) pregnant C3H mice were exposed to 3.43 or 6.68 g Ascorbic Acid/kg bw on the 11th day postcopulation, and to coadministration of a teratogenic dose of cyclophosphamide (CP; 15 mg/kg bw). Sixteen hours after drug administration, embryonal cephalic DNA strand breaks were assessed.…”