Effects of triacetyloleandomycin on the ultrastructure of the rat liver. I. Low dose and early high dose effects

The effects of triacetyloleandomycin (TAO) on liver ultrastructure were studied using an inbred rat strain which was controlled for uniformity of the normal liver ultrastructure. Experimental animals were kept on a highly standardized antioxidant free diet. A high degree of uniformity of TAO induced ultrastructural modifications of the rat liver was obtained, applying perfusion fixation with mixtures containing tris 1 aziridinyl phosphine oxide. A small scale proliferation of the smooth endoplasmic reticulum (SER) was the main effect of a single low dose (100 mg/kg b.w.) administration of TAO. The effects of a single high dose (800 mg/kg b.w.) administration of TAO could be defined at an early stage (up to 24 hr) as the large scale proliferation of SER, the disappearance of a major part of the granular endoplasmic reticulum (GER), and the loss of the typical structure of the nuclear chromatin in experimental hepatocytes. The nucleoli of the hepatocytes and the ultrastructure of the nuclei of cells of the retino endothelial system of the experimental livers remained intact. 800 mg/kg b.w. of TAO produced the formation of lipid inclusions in the hepatocyte cytoplasm in the early period. The bile canaliculi and plasma membranes of the experimental hepatocytes were usually unaltered.