Role of multi-drug resistance-associated protein-1 transporter in statin-induced myopathy.

摘要: This study investigated the effects of probenecid to inhibit multi-drug resistance-associated protein-1 (MRP-1) in mediating efflux and myotoxicity rat skeletal muscles, with administration rosuvastatin. Male Sprague-Dawley rats were administered daily, for 15 days, either rosuvastatin (50, 100 or 200 mg/kg) (100 alone, a combination mg/kg). Skeletal muscle toxicity was elevated mg/kg/day rosuvastatin, elevation creatine kinase by 12-fold, alanine aminotrasferase 10-fold creatinine 9-fold at day 15, no adverse observed when given alone. Mitochondria ultrastructural damage enlargement, disruption, cristolysis vaculation seen soleus plantaris animals high dosages statin. These muscles also expressing more succinic dehydrogenase (SDH)-positive cytochrome oxidase (CyOX)-positive fibers. Although generally well-tolerated, statins produce variety events. Hydrophilic statins, reduced levels non-specific passive diffusion rates into extra-hepatic tissues, are still myopathy. highlights important roles transport mechanisms statin muscles. Excessive influx, two could result cellular resulting toxicity. provides preliminary evidence that MRP-1 transporter possibly play significant statin-induced