Drug-induced morphological alterations in liver

Chronic administration of phenobarbital, an anticonvulsant drug, or rifampicin, an antituberculous drug, alters hepatocyte ultrastructure by inducing the proliferation of smooth endoplasmic reticulum (SER) and changes in glycogen content. While these generalized effects are important, the lobular location of hepatocytes must be considered since pericentral and periportal hepatocytes differ morphologically and most hepatotoxic compounds affect specific zones of the liver. We treated adult male rats with phenobarbital or rifampicin for 5 days to evaluate the effect of each drug on hepatic glycogen levels, glycogen distribution across the liver lobule, and hepatocyte ultrastructure, especially the SER. Our results show a decrease in hepatic glycogen levels as determined biochemically in both treatment groups. Semithin sections of liver specifically stained for glycogen (Figs. 1-3) show that in treated animals glycogen in pericentral and periportal hepatocytes is reduced (Figs. 2,3). Ultrastructurally, periportal hepatocytes typically have clumped glycogen (Fig. 4); however, in treated animals periportal hepatocytes that show the greatest reduction of glycogen contain extensive SER (Fig. 5).