The Effect of β-Carotene Against Adriamycin Toxicity on the Embryo Formation

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 skeletodysgenesis or external malformations

Accumulation of photosensitizer in rat embryos (a spectroscopic study)

The aim of the present study was to investigate the accumulation of photosensitizer Photofrin II in the different organs as well as the placenta and embryos of pregnant rats and to determine during which stage of embryogenesis the photosensitizer is accumulated the most effectively. Materials and methods. The experiments were carried out on 25 fetuses from 10 Wistar rats (weight 160-240 g). Female rats were mated with male rats in the evening. Vaginal smears were collected from each female rat next morning and were examined by microscope in order to determine the presence of sperm. The day when sperm was detected in the vagina was considered to be pregnancy day 0. Photofrin II (a dose of 5 mg/kg) was administered intravenously to pregnant rats on days 7, 14, 16, 18 and 20 of embryogenesis. Rats were euthanized 24 hours after intravenous injection of Photofrin II and the following organs were taken: brain, spleen, liver, kidneys, lungs, uterus, placenta, and embryos. The accumulation of the photosensitizer was observed in the samples prepared from these parts of body. Fluorescence measurements ex vivo were performed with an S2000-FI fluorescence spectrometer (Ocean Optics Inc., Florida, USA) by exciting the samples with a blue light emitting diode (λ=400 nm). Results. A comparative study of fluorescence spectra on days 7, 14, 16, 18 and 20 of embryogenesis showed that the most intense accumulation of Photofrin II in the embryo was on day 7, while on the other days of embryogenesis the accumulation of Photofrin II increased obviously in the uterus and placenta. Conclusions. The obtained data show that the accumulation of Photofrin II in the embryo depended on the stage of embryogenesis as well as on permeability of the placental barrier. Further photodynamic therapy studies are necessary to determine the total effect of Photofrin II on the embryo