Rubratoxin B hepatotoxicity: An electron microscopic study

Rubratoxin B, the principal toxin produced by Penicillium rubrum, causes hepatic damage. The present study describes ultrastructural changes in rat livers at intervals of 3, 6, 24, and 72 hr following administration of 0.36 mg/kg rubratoxin B. Three hours after treatment, minimal ultrastructural changes including loss of glycogen and dilatation of rough endoplasmic reticulum (RER) were observed in groups of hepatocytes. These groups of altered cells showed a random, multifocal pattern of distribution throughout the liver by light and electron microscopy. At 6 hr, hepatocytes in the focal areas affected by rubratoxin showed more severe ultrastructural changes. There was increased vesiculation of RER with loss of ribosomes from the membranes and disaggregation of polyribosome complexes. Mitochondria contained inclusions of cytoplasmic material and intramatrix myelin figures. Increased numbers of lipid droplets were observed in some cells. Sinusoids appeared to be slightly congested. At the 24-hr interval, hepatocytes in the affected areas showed progressive degenerative changes. Mitochondria were extremely swollen and showed loss of cristae and increased numbers of myelin figures in their matrix. Accumulation of cytoplasmic lipid was more evident, and autophagic vacuoles were occasionally seen. Nuclear changes in these hepatocytes included clumping and margination of chromatin. Sinusoids at the 24-hr interval were severely congested with blood cells, platelets, and fibrin. Endothelial cells lining the sinusoids were fragmented and, in some areas, completely absent. By 72 hr, most hepatocytes in the focal, involved areas were completely necrotic. Cytoplasmic organelles showed irreversible, degenerative changes and cell membranes were frequently ruptured. Sinusoids showed complete loss of lining endothelium, and the lumens were occluded with blood cells, fibrin, and cellular debris.