PHARMACOLOGICAL STUDIES

Studies on laboratory animal models of liver intoxication, comparable to the human liver diseases, have been performed in order to prove the hepatoprotective effect of Carsil®.

1. Intoxication with tetrachlormethane: resembles human hepatitis histologically.
On the background of the above intoxication, Carsil® acts through reduction of the liver adipose infiltration, and consolidation of the cell membranes, which results in normalized values of the serum enzyme levels.

2. Intoxication with praseodymium nitrate: resembles the pathoanatomical picture of the human liver adipose infiltration.

Carsil® therapy of the laboratory animals results in a much lower extent of manifestation of the toxic action of praseodymium nitrate, most probably through a consolidation of the membranes of the hepatocytes.

3. Intoxication with ethanol: experimentally induced liver adipose degeneration.

Carsil® administration to the alcohol-treated animals neutralizes to a great extent the toxic effect of the alcohol.

4. Intoxication with phalloidin
Phalloidin has a selective effect on the liver cells, causing a severe impairment of the liver lipid metabolism.

A total or partial normalization of the enzymes' activity is attained after Carsil® administration, with a parallel-reduced lethality of the laboratory animals. The normalization described is more evident with therapeutic administration than with the preventive one.

5. Intoxication with D-galactosamine: the morphological changes resemble human viral hepatitis.
Carsil® has been found to prevent to a considerable extend the D-galactosamine-induced liver toxic changes, i.e. it consolidates the biomembranes in the liver cell, and recovers the normal structure of the latter, and hence the normal metabolism.
In studies of the effect of Carsil® on the synthesis of proteins and microsomal glycoproteins in the liver of mice with experimental galactosamine-induced hepatitis, Tutulkova et al. proved that Carsil® removed the inhibiting effect of galactosamine on the synthesis of proteins and microsomal glycoproteins. The above evidence supports the understanding that Silymarin consolidates the membranes of the liver cells, and restores the normal structure and metabolism of the latter in terms of protein synthesis, glycoprotein and glycogen content, and adipose degeneration. Independently administered, Carsil® does not cause alteration of the enzyme systems of animals with intact liver, and it does not induce ultrastructural changes in the liver cells.