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Skeletal Muscle Susceptibility to Clofibrate Induction of Lesions in Rats

Toxicology Laboratory, Mitsubishi Pharma Corporation, Chiba 292-0818, Japan, Okada.Miyoko{at}mg.m-pharma.co.jp

Yoshimi Inoue

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

Masayuki Ube

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

Fumiko Sano

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

Itsuko Ikeda

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

Jiro Sugimoto

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

Shiro Takagi

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

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.

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Okada, M. Articles by Takagi, S. Search for Related Content PubMed PubMed Citation Articles by Okada, M. Articles by Takagi, S. Social Bookmarking                   What's this?