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Abstract Introduction: Statins are the drug of choice for treatment of hyperlipidemia and prevention of cardiovascular diseases. Treatment with statins dropped off due to adverse effects as hepatotoxicity and myopathy. The purpose of the current study is to make comparison between simvastatin (20 mg/kg) and nano-simvastatin at doses 20mg/kg and 5 mg/kg and to elucidate the synergistic effect of combination of simvastatin (SV), nano-coenzymeQ10 and/or nano-selenium in improving the therapeutic effect and reducing possible side effects. Methods: This study was divided in to two parts; each group contains (8-10) adult albino rats. First part composed of 5 groups; group 1: Rats were received nano-vehicle, group 2: Hyperlipidemic rats were introduced to high fat diet (HFD), group 3: Hyperlipidemic rats treated by simvastatin (20mg/kg) (HFD and SV), group 4: Hyperlipidemic rats treated by nano-simvastatin (20 mg/kg) (HFD and SVNPs20), group 5: Hyperlipidemic rats treated by nano-simvastatin (5 mg/kg) (HFD and SVNPs5), Second part composed of 6 Groups; group 1: Nano-vehicle control group, group 2: Hyperlipidemic rats were introduced to high fat diet (HFD), group 3: Hyperlipidemic rats treated by simvastatin (20mg/kg) (HFD and SV), group 4: Hyperlipidemic rats treated by simvastatin (20 mg/kg) and nano-coQ10 (10 mg/kg) (HFD and SV and coQNPs), group 5: Hyperlipidemic rats treated by simvastatin (20 mg/kg) and nano-selenium (0.1 mg/kg) (HFD and SV and SeNPs), group 6: Hyperlipidemic rats treated by simvastatin (20 mg/kg), nano-coQ10 (10 mg/kg) and nano-selenium (0.1 mg/kg) (HFD and SV and coQNPs and SeNPs). Hyperlipidemia was induced by feeding rats with high fat diet (HFD) for 16 weeks |