Antiinflammatory effect of statins mediated by the reduction of cytokine IL-6 in hepatocytes have been reported. Contrary to beneficial effect, statins can increase susceptibility to mitochondrial dysfunction. Extrahepatic biliary obstruction is associated with oxidative stress, pro-inflammatory response and hepatocyte mitochondrial dysfunction. The aim of our study was to verify the effect of fluvastatin on cholestatic liver injury. Cholestasis was induced in Wistar rats by bile duct ligation. Fluvastatin (1 or 5 mg/kg) was administered after surgery and then daily for 7 days. The dose of 5 mg/kg led to the deterioration of hepatocellular injury. Despite lower production of IL-6, decrease in GSH content, rise of TGFß and inhibition of respiratory complex I in mitochondria were determined. The mRNA expressions of canalicular transporter Mdr1b and basolateral transporter Mrp3 increased in cholestatic liver. Fluvastatin administration then led to the attenuation of this change. Analogously, mRNA expression of conjugative enzyme Ugt1a1 was diminished by fluvastatin administration to cholestatic rats. We can conclude that decrease in the antioxidative status and mitochondrial dysfunction could at least in part participate on the deteriorating effect of fluvastatin. Whether these processes can be a consequence of the alteration in metabolism and transport of potentially toxic substances remains to verify.
- MeSH
- alanintransaminasa krev účinky léků metabolismus MeSH
- alkalická fosfatasa krev účinky léků metabolismus MeSH
- aspartátaminotransferasy krev účinky léků metabolismus MeSH
- bilirubin krev metabolismus MeSH
- gama-glutamyltransferasa krev účinky léků metabolismus MeSH
- glukuronosyltransferasa účinky léků metabolismus MeSH
- glutathion účinky léků metabolismus MeSH
- indoly škodlivé účinky MeSH
- interleukin-6 metabolismus MeSH
- intrahepatální cholestáza farmakoterapie metabolismus MeSH
- játra účinky léků patologie MeSH
- krysa rodu rattus MeSH
- kyseliny mastné mononenasycené škodlivé účinky MeSH
- ligace MeSH
- messenger RNA účinky léků metabolismus MeSH
- potkani Wistar MeSH
- statiny škodlivé účinky MeSH
- transformující růstový faktor beta účinky léků metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
