RESUMO
Megestrol acetate is widely used as an anticancer drug. Recently it has been reported to be hepatogenotoxic in rat and human hepatocytes and forms adducts with rat hepatocytes DNA in vitro or in vivo. In the present study, the toxic effects of megestrol acetate [MA] on the liver of adult female mice and the liver of their fetuses were investigated. The protective role of selenium against MA-induced hepatotoxicity was also investigated. At the zero day of pregnancy, pregnant females were divided into three groups. One group served as a control. The second group received a daily oral dose of 0.4 mg of MA. The third group received selenium in a dose of 1.4 mcg/kg one hour prior to MA. The pregnant females were sacrificed after 20 days of pregnancy and samples were taken from the liver of the females as well as the liver of their fetuses. The tissue samples were processed for electron microscopic studies. The present study showed severe damage of the liver of the adult females following MA administration. This was represented by disorganization of the liver cell plates, inflammation, dilation of the blood sinusoids, multiple foci of degenerated cells, damage of the mitochondria and the endoplasmic reticulum, fluid accumulation in the cells. In addition, marked increase in the lipid dropletes was observed in the hepatocytes while glycogen showed an apparent depletion. The fetal liver also showed an apparent signs of damage which represented by vacuolation of the cell cytoplasm, dilation of the blood sinusoids, mitochondrial and rough endoplasmic reticulum damage, inflammation, and nuclear changes. The results also demonstrate that the use of selenium prior to MA produced protection against MA- induced hepatotoxicity especially in the adult animals