Hepatic fibrosis in biliary-obstructed rats is prevented by Ginkgo biloba treatment

AIM： To assess the antioxidant and antifibrotic effects of long-term Ginkgo biloba administration on liver fibrosis induced by biliary obstruction in rats. METHODS： Liver fibrosis was induced in male Wistar albino rats by bile duct ligation and scission （BDL）. Ginkgo biloba extract （EGb 761, 50 mg/kg.per d） or saline was administered for 28 d. At the end of the treatment period, all rats were killed. Serum aspartate aminotransferase （AST）, alanine aminotransferase （ALT）, and lactate dehydrogenase （LDH） levels were determined to assess liver functions and tissue damage, respectively. Tumor necrosis factor-α （TNF-α） was also assayed in serum samples. Liver tissues were taken for determination of the hepatic malondialdehyde （MDA） and glutathione （GSH） levels, myeloperoxidase （MPO） activity and collagen content. Production of reactive oxidants was monitored by chemiluminescence （CL） assay. Serum AST, ALT, LDH, and TNF-α levels were elevated in the BDL group as compared to control group and were significantly decreased by EGb treatment. RESULTS： Hepatic GSH level, depressed by BDL, was elevated back to control level in EGb-treated BDL group. Increase in tissue MDA level, MPO activity and collagen content due to BDL were also attenuated by EGb treatment. Furthermore, luminol and lucigenin CL values in BDL group increased dramatically compared to control and reduced by EGb treatment. CONCLUSION： Our results suggest that Ginkgo biloba protects the liver from oxidative damage following BDL in rats. This effect possibly involves the inhibition of neutrophil infiltration and lipid peroxidation; thus, restoration of oxidant and antioxidant status in the tissue.

Antioxidants vitamin E and C attenuate hepatic fibrosis in biliary-obstructed rats

AIM： To investigate whether antioxidants vitamin E and C can retard development of hepatic fibrosis in the bilian/obstructed rats. METHODS： Fifty Wistar albino rats were randomly assigned to 5 groups （10 rats in each）. Bile duct was ligated in 40 rats and they were treated as follows： group vitC, vitamin C 10 mg/kg sc daily; group vitE, vitamin E 15 mg/kg sc daily; group vitEC, both of the vitamins; bile duct-ligated （BDL, control） group, physiological saline sc. The fifth group was assigned to sham operation. At the end of fourth week, the rats were decapitated, and hepatic tissue biochemical collagen content and collagen surface area were measured. Hepatic tissue specimens were histopathologically evaluated according to Scheuer system. Serum hyaluronate levels were measured by ELISA method. RESULTS： Despite being higher than sham group, hepatic collagen level was significantly decreased in each of the vitC, vitE and vitEC groups （32.7 ± 1.2, 33.8 ± 2.9, 36.7 ± 0.5 ）μg collagen/mg protein, respectively） compared to BDL （48.3 ± 0.6 mg collagen/g protein） （P 〈 0.001 for each vitamin group）. Each isolated vitamin C, isolated vitamin E and combined vitamin E/C supplementation prevented the increase in hepatic collagen surface density （7.0% ± 1.1%, 6.2% ± 1.7%, 12.3% ± 2.0%, respectively） compared to BDL （17.4% ± 5.6%） （P 〈 0.05 for each）. The same beneficial effect of vitamin C, vitamin E and combined vitamin E/C treatment was also observed on the decrease of serum hyaluronate levels compared to BDL group （P 〈 0.001）. The relative liver and spleen weights, serum transaminases, cholestatic enzymes, bilirubins and histopathological inflammation scores were not different between the antioxidant treatment groups and the control. However, fibrosis staging scores were obviously reduced only in the vitamin E/C combination group （vit EC： 2.4 ± 0.8 vs BDL： 3.1 ± 0.7; P 〈 0.05）. CONCLUSION： Each antioxidant vitamin E, vitamin C and their combination retard hepatic fibrosis in biliary-obstructed rats. Oxidative stress may play a role in the pathogenesis of hepatic fibrosis in secondary biliary cirrhosis.