Fenofibrate-Induced Muscular Toxicity Is Associated with a Metabolic Shift Limited to Type-1 Muscles in Rats
| Autor: | Hiroki Sakai, Jiro Sugimoto, Fumiko Sano, Itsuko Ikeda, Miyoko Okada, Tokuma Yanai, Shiro Takagi |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_specialty Gene Expression PDK4 Biology Toxicology Pathology and Forensic Medicine Necrosis Fenofibrate Internal medicine medicine Animals RNA Messenger Muscle Skeletal Toxicity Tests Chronic Myopathy Molecular Biology Hypolipidemic Agents Soleus muscle Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Cell Biology Lipid Metabolism medicine.disease Fibrosis Rats Cellular infiltration Glucose Muscle Fibers Slow-Twitch Endocrinology Data Interpretation Statistical Toxicity Tensor fasciae latae muscle medicine.symptom Energy source medicine.drug |
| Zdroj: | Toxicologic Pathology. 37:517-520 |
| ISSN: | 1533-1601 0192-6233 |
| DOI: | 10.1177/0192623309336151 |
| Popis: | Morphological changes and mRNA expression levels in type-1 predominant soleus and type-2 predominant tensor fasciae latae muscles of rats treated with fenofibrate were investigated. After fenofibrate by oral gavage at 300 mg/kg/day for 28 days, degeneration/necrosis and regeneration of muscle fibers, cellular infiltration, and fibrosis were seen in soleus muscle. Additionally, expression of PDK4, CPT1-M, CPT2, and FACO mRNAs was increased. In contrast, no morphological changes or mRNA induction were apparent in tensor fasciae latae muscle. These data suggest that sensitivity to fenofibrate-induced muscle toxicity differs among muscles, with only type-1 fibers being susceptible. The up-regulation of PDK4, CPTs and FACO mRNA expression in soleus muscle indicates that the energy source is switched from glucose to fatty acids, and this might be related to the observed fenofibrate-induced muscular toxicity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|