Ultrastructural studies of daunorubicin hepatotoxicity in rats including protective effects of tocopherol and...

The Wistar rats were treated with daunorubicin in the doses corresponding to average doses administered in humans. Analysis under TEM concerned changes in hepatocytes induced by the drug. The changes were compared with those observed in the liver when daunorubicin administration followed protective administration of tocopherol (vitamin E) and ascorbic acid (vitamin C) and when daunorubicin was given simultaneously with tocopherol and ascorbic acid. The results showed nucleus heterochromatin scattering, segregation of nucleolus granular and fibrillar components, swelling of mitochondria and myelin structures in them, segmental degranulation of rough endoplasmic reticulum and decreased number of glycogen granules. The studies led to the conclusion that daunorubicin hepatotoxicity was blunted in animals receiving simultaneously vitamin E and C, which indicates to assume that those antioxidants exert some protective effect on hepatocytes. Normalization of the changes 3 weeks after administration of the last dose suggests that most of the changes are reversible and do not result in chronic liver damage.