The study of the potential importance of pravastatin in the prevention of the cholestatic liver impairment
Abstract
In the present thesis, the effect of pravastatin on the liver damage during chronic obstructive cholestasis was investigated in rats. The decisive fact for choosing pravastatin as a suitable substance for our study was that pravastatin has already shown positive effects in several patients with cholestasis and its hydrophilic nature does not require metabolism in impaired liver and allows compensatory excretion in the kidney.
Detailed elucidation of pravastatin effect on development of liver injury during bile duct obstruction in rats was performed using complex biochemical and histological examinations together with the evaluation of changes in enzyme and transport mechanisms for bile acids (BA), bilirubin, cholesterol, and iron. Administration of pravastatin to animals with bile duct obstruction induced significant changes, which, however, differed accordingly to the dose applied (1 or 5 mg/kg/day).
While in group with 1mg/kg of pravastatin both decrease in plasma concentrations of BA, bilirubin, and cholesterol and attenuation of proliferative and fibrotic changes were observed, in the group with higher dose of pravastatin an increased mortality and worsening of biochemical and histological parameters were noted when compared with BDO animals. The acquired data enabled to summarize the potentially beneficial effect of pravastatin on the liver damage induced by obstructive cholestasis.
The choice of proper drug dose seems to be entirely fundamental. The effect itself includes a number of regulatory and executive mechanisms and is not associated with hypocholesterolemic effect of the drug.
So we can classify this effect as so-called pleiotropic effect of the statins.