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

Abstract

AIM:To investigate whether antioxidants vitamin E and C can retard development of hepatic fibrosis in the biliary-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.

Modulation of extracellular matrix by nutritional hepatotrophic factors in thioacetamide-induced liver cirrhosis in the rat

“…Virus therapy (adenovirus containing MMP-1) obtained a lower reduction of hepatic collagen (15 to 5%); however, the ALT level increased, indicating hepatocyte damage (19). Other substances have proven to be effective: vitamins C, E and C + E (24), losartan (28), gliotoxin (24), pirfenidone (29), relaxin (30), and Han-Dan-Gan-Lee (31) also reduced fibrosis in rat livers. Hepatic growth factor (22), halofuginone (32) and adenovirus with urokinase plasminogen activator (25) induced collagen reduction in cirrhosis models.…”

Image Analysis Tools for Evaluation of Microscopic Views of Immunohistochemically Stained Specimen in Medical Research–a Review

“…To investigate whether antioxidants vitamin Z and vitamin C could retard development of hepatic fibrosis, Soylu et al [25] carried out histological analysis of liver tissue using SAMBA software to determine the collagen content. A custom made program was developed to automatically outline and measure the collagen area and the total liver area.…”

Vitamin E Supplementation Modulates Endotoxin-induced Liver Damage in a Rat Model

“…Vitamin E (-Tocopherol [(-Toc]) is the primary membrane bound, lipid-soluble, chain-breaking antioxidant that protects cell membranes against lipid peroxidation [15][16][17][18]. Vitamin E pre-treatment has been reported to be beneficial in preventing formaldehyde-induced tissue damage in rats [16,19].…”