Poster Presenter

Effects of Fluvastatin on the Liver Injured by Experimental Cholestasis
Halka Lotkova, Pavla Stankova, Tomas Rousar, Otto Kucera, Lukas Kohoutek, Zuzana Cervinkova
Czech Republic

Beyond hypocholesterolemic effect, antiinflammatory action of statins mediated by the reduction of IL-6 in hepatocytes have been reported. Contrary to beneficial effect, statins can increase susceptibility to mitochondrial dysfunction thus leading to cell death. Extrahepatic biliary obstruction is associated with oxidative stress and pro-inflammatory response. The aim of our study was to verify the effect of fluvastatin on cholestatic liver injury.

Male Wistar albino rats (320 - 380 g) were used. Cholestasis was induced by bile duct ligation. Fluvastatin (1 or 5 mg/kg) was administered immediately after surgery and then daily for 7 days.

Liver injury (ALT, AST) and cholestasis (ALP, GGT, bilirubin) were determined in the serum. In the liver, glutathione and inflammatory cytokines (TNF-α, IL-6) were measured. Parameters of energy metabolism in liver mitochondria were assessed using high-resolution respirometry. Histological preparatives of the liver tissue were evaluated.

Bile duct ligation caused increase in ALT, AST, ALP, GGT and bilirubin in the serum; IL-6 and MDA were increased in the liver. Fluvastatin - 5 mg/kg led to attenuation of IL-6 production; ALT, AST and mitochondrial dysfunction were deteriorated.

Despite of attenuating effect on inflammatory marker IL-6, deleterious effect of fluvastatin was observed in the liver.

Acknowledgement: Supported by grant NS/9739-3/2008.