Cytogenetic and Ultrastructural Studies of Effects of Antifungal Drug, Fluconazole on Liver of New-born Mice

Abstract

As a potent antifungal drug, fluconazole clinically used to eradicate both systemic and superficial mycoses resulting in hepatotoxicity. The objective of the current study was to evaluate hepatotoxicity and genotoxicity in newborn male mice. Mice were treated orally with 0.5 ml fluconazole doses of (0, 25, 50, and 100 mg/kgbw) per day for five consecutive weeks. Micronucleus test, chromosomal aberrations in bone marrow cells, histopathological investigation and DNA fragmentation in the liver tissue was done. Micronuclei are significantly noticed in bone marrow cells of mice given 50 and 100 mg/kgbw fluconazole however, there is no effect on the genotoxicity induced by 25 mg/kgbw dose of fluconazole. A dose-dependent and significant increase in structural and numerical chromosomal aberrations were detected in the 50 and 100 mg/kgbw fluconazole-treated group but a 100 mg/kg was highly significant. The chromosomal aberrations were manifested in hypoploidy, deletion, centric fusion and stickiness. Besides, hepatocellular massive infiltration, cytoplasmic vacuolation, congestion and dilatation in the central veins were seen in 50 and 100 mg/kgbw fluconazole. Interestingly, 25mg/kgbw fluconazole-treated mice showed mild hepatocellular degeneration. Consequently, these findings confirmed that fluconazole to a greater extent was a potent hepatotoxic drug <i>in vivo</i> in newborn mice.