Malformations Induced in Pregnant Rats and their Fetuses Treated with Fluconazole and / or Gamma Radiation

The purpose of the present work is to study the synergistic effect of antifungal (fluconazole) treatment and / or gamma-radiation stress on pregnant mothers and their developing embryos by evaluating the maternal biochemical changes, embryological and histopathological lesions. Fluconazole is a broad-spectrum azole antifungal medication used for the treatment of several types of fungal infections including common forms such as vaginal candidiasis. Fluconazole (50 mg/kg b.wt.) was daily administered by oral gavage to pregnant rats from the 4th to the 13th gestational days during which they were subjected to gamma-radiation at a dose level of 1Gy given at the 6th day (post implantation period) and 1Gy on the 12th day (organogenesis period) of gestation. The animals were dissected and examined on the 20th day of gestation (one day prior to praturation). Fluconazole and radiation dual treatment resulted in increased maternal serum of lactate dehydrogenase (LDH), creatine phosphokinase (CPK), aspartate transaminase (AST) activities and sodium (Na+) level accompanied with a decline in potassium (K+) concentration. The results showed that there was an elevation in the lipid peroxidation end product malondialdehyde (MDA) as well as nitric oxide (NO) in the brain and heart tissues of pregnant rats. Meantime, the developing embryos in the uteri showed various teratological, skeletal and histological impairments. Moreover, the fluconazole treatment and / or gamma-radiation harm effects were detected as growth retardation, malformations, intrauterine death and embryonic resorption. The examination of the endoskeletal system of fetuses showed retardation in the ossification of the skull bones and lack of ossification at the center of vertebrae and appendages. In addition, the embryonic histological examinations revealed heart loss of normal architecture, the interstitial tissues were oedematous and containing necrotic cellular debris together with fibrosis of nerve cells in the brain of fetuses.