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Toxicologic Pathology
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Journal Article

Neuronal and Muscular Inclusions in Rats with Hindlimb Dysfunction after Treating with Difluorobenzhydrylpiperadine

Yoshihiro Yamanaka

Institute for Biomedical Research, Teijin Ltd., 4-3-2 Asahigaoka, Hino 191, Japan, Department of Pathobiology, Nihon University School of Veterinary Medicine, 1866 Kameino, Fujisawa 252, Japan

Tetsu Shimada

Department of Pathobiology, Nihon University School of Veterinary Medicine, 1866 Kameino, Fujisawa 252, Japan

Rika Mochizuki

Department of Pathobiology, Nihon University School of Veterinary Medicine, 1866 Kameino, Fujisawa 252, Japan

Yoko Suzuki

Department of Pathobiology, Nihon University School of Veterinary Medicine, 1866 Kameino, Fujisawa 252, Japan

Kazuya Takenouchi

Institute for Biomedical Research, Teijin Ltd., 4-3-2 Asahigaoka, Hino 191, Japan

Toshiaki Takeda

Institute for Biomedical Research, Teijin Ltd., 4-3-2 Asahigaoka, Hino 191, Japan

Hiroshi Uno

Institute for Biomedical Research, Teijin Ltd., 4-3-2 Asahigaoka, Hino 191, Japan

Yoshihiro Izawa

Institute for Biomedical Research, Teijin Ltd., 4-3-2 Asahigaoka, Hino 191, Japan

Kosaku Fujiwara

Department of Pathobiology, Nihon University School of Veterinary Medicine, 1866 Kameino, Fujisawa 252, Japan

Rats showing an ataxic gait induced by 20 wk of treatment with 0, 30, or 60 mg/kg of difluorobenzhydrylpiperadine (DFBP), a detriazinyl metabolite 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.

Key Words: Almitrine • cationic amphiphilic drug • detriazinyl metabolite • drug-induced lipidosis • lamellar body • lysosome • neurotoxicity

Toxicologic Pathology, Vol. 25, No. 2, 150-157 (1997)
DOI: 10.1177/019262339702500204
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