Ultrastructural and Biochemical Alterations of Livers from Rats Treated With 5,5-Diphenyl-2-thiohydantoin (DPTH) and Thyroxine

Summary

The ultrastructure and chemical composition of rat livers were examined after the animals were fed 5,5-diphenyl-2-thiohydantoin (DPTH) and/or injected with L-thyroxine (T₄). Mitochondria from T₄-treated rats were more numerous (with respect to normal livers) and were larger with extremely electron-lucent matrices. That glycogen was radically reduced in the livers of T₄-treated animals was confirmed by both electron microscopic and biochemical analysis. Cisternae of the RER were usually non-parallel and somewhat dilated. No other ultrastructural changes were easily discernible. Analysis for lipid and RNA content showed small increases on a wet weight basis. DPTH caused significant ultrastructural changes which included proliferation of the SER and the appearance of electron-lucent matrices in mitochondria, absence of mitochondrial granules and, in some cells, appearance of myelin figures. In addition, DPTH was shown to block conversion of acylcarnitines to ketone bodies by mitochondria in vitro and in vivo. The T₄-stimulated increase in RNA content was also inhibited by DPTH. Both electron microscopy and biochemical analysis showed that DPTH caused lipid accumulation and prevented the T₄-stimulated decrease in glycogen content. The pattern of alterations of the liver as seen by electron microscopy and biochemical analysis correlated well.