The influence of rosuvastatin on liver microsomal CYP2C6 in hereditary hypertriglyceridemic rat
Jazyk angličtina Země Švédsko Médium print
Typ dokumentu časopisecké články
PubMed
23353843
PII: NEL330912A06
Knihovny.cz E-zdroje
- MeSH
- aromatické hydroxylasy antagonisté a inhibitory metabolismus MeSH
- cholesterol dietní farmakologie MeSH
- cytochrom P450 CYP2C9 MeSH
- fluorbenzeny farmakologie MeSH
- genetická transkripce účinky léků MeSH
- hyperlipoproteinemie typ IV farmakoterapie genetika metabolismus MeSH
- jaterní mikrozomy účinky léků enzymologie MeSH
- krysa rodu Rattus MeSH
- lidé MeSH
- messenger RNA metabolismus MeSH
- mutantní kmeny potkanů MeSH
- potkani Wistar MeSH
- pyrimidiny farmakologie MeSH
- regulace genové exprese enzymů účinky léků MeSH
- rodina 2 cytochromů P450 MeSH
- rosuvastatin kalcium MeSH
- statiny farmakologie MeSH
- steroid-21-hydroxylasa antagonisté a inhibitory genetika metabolismus MeSH
- sulfonamidy farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- aromatické hydroxylasy MeSH
- cholesterol dietní MeSH
- Cyp2c6v1 protein, rat MeSH Prohlížeč
- CYP2C9 protein, human MeSH Prohlížeč
- cytochrom P450 CYP2C9 MeSH
- fluorbenzeny MeSH
- messenger RNA MeSH
- pyrimidiny MeSH
- rodina 2 cytochromů P450 MeSH
- rosuvastatin kalcium MeSH
- statiny MeSH
- steroid-21-hydroxylasa MeSH
- sulfonamidy MeSH
OBJECTIVES: The aim of this study was to investigate whether rosuvastatin affects expression and activity of rat CYP2C6. This cytochrome P450 is considered to be a counterpart of human CYP2C9, which metabolizes many drugs, including diclofenac, ibuprofen or warfarin. DESIGN: Male hereditary hypertriglyceridemic (HHTg) rats were fed standard laboratory diet (STD) or high cholesterol diet (HCD: STD + 1% of cholesterol w/w + 10% of lard fat w/w) for 21 days. A third group of rats were fed high a cholesterol diet with rosuvastatin added (0.03% w/w). Expression of CYP2C6 was measured in liver samples using real-time PCR (mRNA level) and Western blotting (protein level). Formation of diclofenac metabolites (typical enzyme activity of CYP2C6) was analyzed using HPLC with UV detection. RESULTS: Administration of rosuvastatin to HHTg rats resulted in significantly increased mRNA expression and enzyme activity in HCD-fed animals; changes of CYP2C6 protein were non-significant. These results suggest that CYP2C6 expression and activity are positively affected by rosuvastatin in hereditary hypertriglyceridemic rats after intake of HCD. CONCLUSION: The results presented open the possibility that in humans, rosuvastatin may affect the metabolism of many drugs by influencing expression and activity of CYP2C6 (counterpart of human CYP2C9). Further studies are needed to elucidate the effects of this statin on CYP2C9 in humans.