engleski

An experimental transplacental genotoxicity model of fluconazole

Chemical genotoxicity is evaluated using batteries of senstive test. However, not a single test does evaluate transplacental genome damage in young organisms. The aim of this study was to develop a model for testing transplacental cytogenetic damage in newborn and three-week old mice. The model comprises biochemical (glutathione peroxidase (gpx), malonaldehyde (mda)), genotoxic (in vivo micronucleus) and histological (apoptosis) levels. Dams (Balbc/c) were exposed to physiological saline (PS), cyclophosphamide (CP) (10mg/kg) and fluconazole (FN) (12 mg/kg). The compounds were administered i.p. in three consecutive daily doses on days 12-14 of pregnancy. Blood samples were taken before and after the treatment (48h after initial dose). Neonatal genotoxicity in pups was analysed from 6-18h after delivery and tissues were taken for analysis. Late genotoxic effects were investigated using the challenge assay in pups administered CP on day 19 of birth. Blood was sampled before and 48h after treatment. MN frequency in dams was significantly above the control values in the CP treated group. In the groups treated with PS and FN there were no significant differences. In the neonatal pups a significant increase in MN frequency was observed in the neonates from dams treated with CP and FN was detected. These significant increases in frequency of MN sustained without change in pups until the day 19 after delivery. The CP challenge assay showed potency to distinguish difference in repair capacity possibly caused by intrauterine exposure. Significant decreases in the concentrations of mda and gpx in the livers of neonatal pups in groups treated with CP and FN were detected . Animals treated with CP and FN showed no differences in the number of renal and hepatic apoptotic cells. The pilot study results indicate the importance of the model for testing the transplacental genotoxicity of chemical agents.

transplacental; fluconazole; genotoxicity

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