ABSTRACT
Rats showing an ataxic gait induced by 20 wk of treatment with 0, 30, or 60 mg/kg of difluorobenzhydrylpiperadine (DFBP), a detriazinyl metabolic of almitrine, were examined by light microscopy and transmission electron microscopy. Vacuolar degeneration associated with lamellar inclusions was observed in musculus soleus and m. interossei of the hindlimbs in DFBP-treated rats. The inclusions were also produced within sensory neurons, satellite and Schwann cells, and vascular endothelial cells of thoracic and lumbar dorsal root ganglia as well as muscle spindles of affected muscles. Membrane-bound vacuoles containing electron-dense granules were seen in the peripheral nerves. This study demonstrated neuronal and muscular toxicity of DFBP in rats.
Subject(s)
Almitrine/analogs & derivatives , Almitrine/metabolism , Almitrine/toxicity , Ataxia/chemically induced , Hindlimb/physiopathology , Inclusion Bodies/pathology , Muscle, Skeletal/pathology , Neurons/pathology , Peripheral Nerves/pathology , Animals , Inclusion Bodies/drug effects , Inclusion Bodies/ultrastructure , Male , Muscle, Skeletal/drug effects , Muscle, Skeletal/ultrastructure , Neurons/drug effects , Neurons/ultrastructure , Peripheral Nerves/drug effects , Peripheral Nerves/ultrastructure , Rats , Rats, Inbred F344ABSTRACT
Toxic effects of a detriazinyl metabolite of almitrine (DTMA) were evaluated in rats and on cultured rat macrophages. In rats daily treated with DTMA for 16 weeks, spastic gaits with heel-lifting appeared, and lamellated and/or crystalloid bodies formed in sensory neurons, satellite cells, Schwann cells, and vascular endothelial cells of the dorsal root ganglia. The lysosomal lamellated bodies, which were not induced by almitrine, were produced also in cultured rat macrophages exposed to over 1 x 10(-5) M DTMA.
