Linked Life Data

18509883

Source:http://linkedlifedata.com/resource/pubmed/id/18509883

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15-16
pubmed:dateCreated
2008-5-27
pubmed:abstractText
This study investigated the effects of probenecid to inhibit the multi-drug resistance-associated protein-1 (MRP-1) in mediating the efflux and myotoxicity in rat skeletal muscles, with administration of rosuvastatin. Male Sprague-Dawley rats were administered daily, for 15 days, with either rosuvastatin (50, 100 or 200 mg/kg) or probenecid (100 mg/kg) alone, or with a combination of rosuvastatin (50, 100 or 200 mg/kg) and probenecid (100 mg/kg). Skeletal muscle toxicity was elevated with probenecid administered with 200 mg/kg/day of rosuvastatin, with the elevation of creatine kinase by 12-fold, alanine aminotrasferase by 10-fold and creatinine by 9-fold at day 15, with no adverse effects observed when probenecid was given alone. Mitochondria ultrastructural damage with enlargement, disruption, cristolysis and vaculation was seen in the soleus and plantaris of animals administered with probenecid and high dosages of statin. These muscles were also expressing more succinic dehydrogenase (SDH)-positive and cytochrome oxidase (CyOX)-positive fibers. Although generally well-tolerated, statins produce a variety of adverse skeletal muscle events. Hydrophilic statins, with reduced levels of non-specific passive diffusion rates into extra-hepatic tissues, are still seen to produce myopathy. This highlights the important roles of transport mechanisms in statin transport at the skeletal muscles. Excessive influx, reduced efflux or the combination of the two could result in elevated cellular levels of statins at the skeletal muscles, resulting in toxicity. This study provides preliminary evidence that the MRP-1 transporter and efflux at skeletal muscles possibly play significant roles in statin-induced myopathy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0024-3205
pubmed:author
pubmed:issnType
Print
pubmed:day
9
pubmed:volume
82
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
823-30
pubmed:meshHeading
pubmed-meshheading:18509883-Animals, pubmed-meshheading:18509883-Body Weight, pubmed-meshheading:18509883-Electron Transport Complex IV, pubmed-meshheading:18509883-Fluorobenzenes, pubmed-meshheading:18509883-Hydroxymethylglutaryl-CoA Reductase Inhibitors, pubmed-meshheading:18509883-Male, pubmed-meshheading:18509883-Microscopy, Electron, Transmission, pubmed-meshheading:18509883-Mitochondria, Muscle, pubmed-meshheading:18509883-Multidrug Resistance-Associated Proteins, pubmed-meshheading:18509883-Muscle, Skeletal, pubmed-meshheading:18509883-Muscle Weakness, pubmed-meshheading:18509883-Muscular Diseases, pubmed-meshheading:18509883-Paraffin Embedding, pubmed-meshheading:18509883-Probenecid, pubmed-meshheading:18509883-Pyrimidines, pubmed-meshheading:18509883-Rats, pubmed-meshheading:18509883-Rats, Sprague-Dawley, pubmed-meshheading:18509883-Renal Agents, pubmed-meshheading:18509883-Sulfonamides
pubmed:year
2008
pubmed:articleTitle
Role of multi-drug resistance-associated protein-1 transporter in statin-induced myopathy.
pubmed:affiliation
Pharmacogenetics Laboratory, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
pubmed:publicationType
Journal Article