Hepatocyte mitochondrial alterations in griseofulvin fed mice

Ultrastructural changes in mitochondria from hepatocytes of male Swiss Webster mice were observed during the course of porphyria induced by ingestion of a powdered diet containing 2.5 percent griseofulvin (GF). A variety of sporadic mitochondrial alterations were noted between three days and 22 weeks. Mitochondria appeared intact in hepatocytes from control mice fed powdered diet alone. The abundance and prominence of altered mitochondria increased after seven weeks and was particularly apparent after 15 weeks, concurrent with pronounced hepatomegaly and Mallory body (MB) formation. One or more changes observed in some mitochondria of several hepatocytes included: swelling, associated myelin bodies, increased matrix density, disoriented cristae, intracristal swelling, bizarre shapes, paracrystalline inclusions and elongated or spherulated giant forms. Many mitochondria showed intimate association with rough surface endoplasmic reticulum (RER) adjacent to smooth surface endoplasmic reticulum (SER). GF-induced mitochondrial defects appear to represent nonspecific morphologic alterations similar to many reported in human hepatocytes in alcoholic liver disease, porphyria and various other toxic and metabolic liver diseases. They may reflect another common site of metabolic insult between two such diverse processes as GF-induced mouse porphyria and human alcoholic liver disease.