Cell-specific toxicity of fibrates in human embryonal rhabdomyosarcoma cells
| Autor: | Takayoshi Maiguma, Ryozo Oishi, Daisuke Teshima, Koji Fujisaki, Yoshinori Itoh, Toshiyuki Sasaguri, Fumi Takahashi-Yanaga, Kazutaka Makino |
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| Rok vydání: | 2003 |
| Předmět: |
Simvastatin
medicine.medical_specialty Time Factors Receptors Cytoplasmic and Nuclear Pharmacology Biology Clofibric Acid Fenofibrate Internal medicine Tumor Cells Cultured medicine Humans Gemfibrozil Rhabdomyosarcoma Embryonal Clofibrate RNA Messenger Viability assay Receptor Hypolipidemic Agents Bezafibrate Reverse Transcriptase Polymerase Chain Reaction Fibric Acids Drug Synergism General Medicine Disease Models Animal Endocrinology Ciprofibrate Transcription Factors medicine.drug |
| Zdroj: | Naunyn-Schmiedeberg's Archives of Pharmacology. 367:289-296 |
| ISSN: | 0028-1298 |
| DOI: | 10.1007/s00210-002-0660-9 |
| Popis: | The effects of a variety of fibrates on the cell viability were examined in human embryonal rhabdomyosarcoma cells (HRMSC). Five fibrates, including fenofibrate, clofibrate, gemfibrozil, bezafibrate and ciprofibrate, all concentration-dependently reduced the cell viability determined by the mitochondrial enzyme activity. The cell injury occurred time-dependently and was marked at 24-48 h. The toxic action of fibrates was specific to HRMSC, since bezafibrate did not induce any marked changes in the viability of human microvascular endothelial cells or arterial smooth muscle cells. Synergistic cell injury was observed after a combined treatment with bezafibrate and simvastatin, although simvastatin alone reduced the cell viability. The cell injury was characterized by a typical nuclear damage, as evidenced by Hoechst 33342 staining and deoxynucleotidyl transferase dUTP nick-end label-positive staining. Similar cell-specific injury was induced by 8(S)-hydroxyeicosatetraenoic acid, a potent peroxisome proliferator-activated receptor alpha (PPARalpha) agonist. Consistent with these data, a marked expression for PPARalpha mRNA was observed in HRMSC but not in the endothelial or smooth muscle cells. Therefore, it is suggested that fibrates cause a cell-specific injury in HRMSC via activation of PPARalpha. Moreover, our present cell injury model using HRMSC may be useful for elucidating the mechanisms of clinical rhabdomyolysis induced by lipid-lowering agents. |
| Databáze: | OpenAIRE |
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