Crystalloid Inclusions in Hepatocyte Mitochondria of Dogs Treated with Levamisole

Intramitochondrial crystalloid inclusions were seen in about 10% of the hepatic cells of four dogs treated with levamisole. Three degrees of severity of mito­ chondrial alteration occurred. Mild changes consisted of condensation of mitochondrial matrix into electron-opaque clumps. The intermediate stage was manifested as well­ developed crystalloid inclusions composed of bundles of parallel fibers. Such fibers might be tubular structures. Severe alteration was characterized by a markedly elongated crystalloid inclusion that caused the involved mitochondrion to be greatly enlarged. Intramitochondrial crystalloid inclusions have been seen in the livers of several animal species. Mitochondria of livers of swine fed lead acetate (15) and of rats in ammonium intoxication (2) contained lamellar formations. Intramitochondrial inclusions have been seen in hepatocytes of normal and alcohol-fed monkeys (I I, 14). Similar inclusions have been seen in mito­ chondria of the livers of healthy and diseased humans (4,5). Inclusions have also been seen in mitochondria of hepatocytes of untreated dogs (10), and in dogs treated with 2, sulfanylamido-3-methoxy pyrazine (8). Degeneration of both inclusions and involved mitochondria occurs in dogs subjected to in vivo ischemia (9). Although intramitochondrial crystalloid inclusion formation can be induced experimentally in animals by the use of chemicals (2, 8, 15), the various stages of mitochondrial alterations that occur in crystalloid forma­ tion have not been described. The several stages of inclusion body formation were observed in the present study in which dogs were treated with levamisole (American Cyanamid Co., Princeton, N. J.). This drug has been used experi­ mentally in dogs as a microfilaricide in infections by Dirofilaria irnmitis (I).