Cell-specific toxicity of fibrates in human embryonal rhabdomyosarcoma cells

作者: Takayoshi Maiguma , Koji Fujisaki , Yoshinori Itoh , Kazutaka Makino , Daisuke Teshima

DOI: 10.1007/S00210-002-0660-9

关键词: ClofibrateGemfibrozilCiprofibrateEndocrinologyInternal medicineViability assaySimvastatinBiologyReceptorFenofibrateBezafibratePharmacology

摘要: The effects of a variety 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 determined by mitochondrial enzyme activity. injury occurred time-dependently was marked at 24–48 h. toxic action specific to HRMSC, since did not induce any changes microvascular endothelial or arterial smooth muscle cells. Synergistic observed after combined treatment with simvastatin, although simvastatin alone viability. characterized typical nuclear damage, as evidenced Hoechst 33342 staining deoxynucleotidyl transferase dUTP nick-end label-positive staining. Similar cell-specific induced 8(S)-hydroxyeicosatetraenoic acid, potent peroxisome proliferator-activated receptor α (PPARα) agonist. Consistent these data, expression for PPARα mRNA HRMSC but Therefore, it is suggested that cause via activation PPARα. Moreover, our present model using may be useful elucidating mechanisms clinical rhabdomyolysis lipid-lowering agents.

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