Adriamycin is an anthracycline antibiotic widely used for the treatment of many types of cancer. The cytotoxic effect of Adriamycin occurs by a free radical-mediated mechanism. Thus, to prevent or reduce the toxic effect of Adriamycin, it is possible to use it in combination with antioxidants. The aim of this study was to evaluate a potential effect of β-carotene against Adriamycin-induced toxicity on the embryo formation.
Materials and methods: Pregnant rats were treated with Adriamycin, β-carotene, and their combination during the critical stages of embryogenesis. The first group was control group. Adriamycin was administered on day 9 (group 2a) and day 12 (group 2b) of gestation by a single intraperitoneal injection at a dose of 5 mg/kg. β-Carotene was given at a dosage of 0.6 mg/(kg·day) from day 6 to 10 or from day 9 (group 3a) to 13 (group 3b) of gestation 5 times per os; in the case of their combination, β-carotene was given per os 3 times before Adriamycin injection, one time simultaneously with Adriamycin and one time after its injection (groups 4a and 4b). Animals were euthanized on day 21 of gestation. Embryo resorptions and alive fetuses were counted, weighed, and measured. The embryos of each litter were examined macroscopically after the Buen solution fixation for the embryo defects. In order to render the skeleton visible, the soft tissues were macerated using caustic soda, stained with alizarin red, and cleared with glycerin.
Results: Adriamycin induced embryotoxicity; the combination of Adriamycin and β-carotene decreased the number of Adriamycin-induced embryo resorptions about two times. A gavage with Adriamycin alone decreased fetal body weights (P<0.05), while giving it in combination, the fetal body weight was similar to that in the control group. Adriamycin induced the retardation of skeletogenesis and external fetal malformations (microphthalmia, hydrocephaly, anencephaly, and others). After an exposure to β-carotene, external malformations (diaphragmatic hernia) of embryos were found only occasionally. β-Carotene in combination with Adriamycin produced no positive effect on Adriamycin-induced skeletodysgenesis or external malformations.
Conclusions: Antioxidant β-carotene in combination with Adriamycin slightly reduced the Adriamycin-induced embryotoxicity, but produced no positive effect on Adriamycin-induced skeleto-dysgenesis or external malformations.