In:
Basic & Clinical Pharmacology & Toxicology, Wiley, Vol. 103, No. 5 ( 2008-11), p. 476-481
Abstract:
Abstract: 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 CCl 4 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‐β (TGF‐β) was determined by Western blot and quantified densitometrically. Alkaline phosphatase, γ‐glutamyl transpeptidase and alanine aminotransferase increased in the group receiving CCl 4 ; trolox completely or partially prevented these alterations. Glycogen was almost depleted by CCl 4 but was partially preserved by trolox. Lipid peroxidation increased while glutathione decreased by CCl 4 administration; trolox corrected both effects. Histology showed thick bands of collagen, necrosis and distortion of the hepatic parenchyma in the CCl 4 group, such effects were prevented by trolox. Hydroxyproline content increased 5‐fold by CCl 4 , while the group receiving both CCl 4 and trolox showed no significant difference compared to the control group. CCl 4 increased 3‐fold TGF‐β, while trolox completely prevented this increase. We found that trolox effectively prevented cirrhosis induced with CCl 4 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‐β expression.
Type of Medium:
Online Resource
ISSN:
1742-7835
,
1742-7843
DOI:
10.1111/pto.2008.103.issue-5
DOI:
10.1111/j.1742-7843.2008.00324.x
Language:
English
Publisher:
Wiley
Publication Date:
2008
detail.hit.zdb_id:
2151592-X
detail.hit.zdb_id:
2134679-3
SSG:
15,3
