Cirrhosis is a very common disease and its treatment is limited due to lack of effective drugs. Some studies indicate that this disease is associated with oxidative stress. Therefore, we decided to study the effect of
trolox, an effective
antioxidant, on experimental
cirrhosis.
Cirrhosis was induced by CCl4 administration (0.4 g/kg, intraperitoneally, three times per week, for 8 weeks) to Wistar male rats.
Trolox was administered daily (50 mg/kg, orally).
Fibrosis was assessed histologically and by measuring liver
hydroxyproline content.
Glutathione, lipid peroxidation and
glycogen were measured in liver;
serum markers of liver damage were also quantified.
Transforming growth factor-beta (
TGF-beta) was determined by Western blot and quantified densitometrically.
Alkaline phosphatase,
gamma-glutamyl transpeptidase and
alanine aminotransferase increased in the group receiving CCl4;
trolox completely or partially prevented these alterations.
Glycogen was almost depleted by CCl4 but was partially preserved by
trolox. Lipid peroxidation increased while
glutathione decreased by CCl4 administration;
trolox corrected both effects. Histology showed thick bands of
collagen,
necrosis and distortion of the hepatic parenchyma in the CCl4 group, such effects were prevented by
trolox.
Hydroxyproline content increased 5-fold by CCl4, while the group receiving both CCl4 and
trolox showed no significant difference compared to the control group. CCl4 increased 3-fold
TGF-beta, while
trolox completely prevented this increase. We found that
trolox effectively prevented
cirrhosis induced with CCl4 in the rat. Our results suggest that the beneficial effects of
trolox may be associated to its
antioxidant properties and to its ability to reduce the profibrogenic
cytokine TGF-beta expression.