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Toxicologic Pathology
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Skeletal Muscle Susceptibility to Clofibrate Induction of Lesions in Rats

Miyoko Okada
Yoshimi Inoue
Masayuki Ube
Fumiko Sano
Itsuko Ikeda
Jiro Sugimoto
Shiro Takagi

Toxicology Laboratory, Mitsubishi Pharma Corporation, Chiba 292-0818, Japan

Correspondence: Address correspondence to: Miyoko Okada, Mitsubishi Pharma Corporation, 1-1-1, Kazusakamatari, Kisarazu, Chiba 292-0818, Japan; e-mail:Okada.Miyoko{at}mg.m-pharma.co.jp

Morphological changes induced by clofibrate in type-1 predominant soleus, type-2 predominant tensor fasciae latae, and type-1 and -2 mixed biceps femoris muscles and diaphragm in rats were investigated. Administration of the agent at 500 or 750 mg/kg/day by oral gavage for 14 or 28 days caused lesions in the soleus muscle and diaphragm, bur no changes in the tensor fasciae latae and biceps femoris muscles. In soleus muscle, vacuolation of muscle fibers was observed in all animals treated with clofibrate, and degeneration of muscle fibers and infiltration of leukocytes were noted at 750 mg/kg/day. In diaphragm, vacuolation of muscle fibers was also observed in all animals treated with clofibrate, and these lesions were located in type-1 skeletal muscles densely stained with NADH-TR. The vacuoles seen in soleus muscle and diaphragm were positive for oil red O staining. In addition, increase of lipid droplets and mitochondrial hypertrophy was seen in soleus muscle, ultrastructurally. These data suggest that sensitivity to clofibrate-induced muscle toxicity differs among muscles, with type-1 fibers being susceptible.

Key Words: Clofibrate • rat • muscle • myopathy • type-1 • mitochondria

Toxicologic Pathology, Vol. 35, No. 4, 517-520 (2007)
DOI: 10.1080/01926230701338925
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 Toxicol PatholHome page
M. Okada, F. Sano, I. Ikeda, J. Sugimoto, S. Takagi, H. Sakai, and T. Yanai
Fenofibrate-Induced Muscular Toxicity Is Associated with a Metabolic Shift Limited to Type-1 Muscles in Rats
Toxicol Pathol, June 1, 2009; 37(4): 517 - 520.
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