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    Antioxidants vitamin E and C attenuate hepatic fibrosis in biliary-obstructed rats
    (W J G Press, 2006) Soylu, Ali Riza; Aydogdu, Nurettin; Basaran, Umit Nusret; Altaner, Semsi; Tarcin, Orhan; Gedik, Nursal; Umit, Hasan
    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 mu g 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. (C) 2006 The WJG Press. All rights reserved.
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    Effects of vitamins E and C supplementation on hepatic glutathione peroxidase activity and tissue injury associated with ethanol ingestion in malnourished rats
    (Elsevier Science Inc, 2006) Soylu, Ali Riza; Altaner, Semsi; Aydogdu, Nurettin; Basaran, Umit Nusret; Tarcin, Orhan; Gedik, Nursal; Umit, Hasan
    Background: Oxidative stress has been associated with tissue injury in alcoholic liver disease. Although this close association is well known, whether prevention of oxidative stress retards tissue injury has not been thoroughly investigated. Objective: The aim of this study was to determine the effects of supplementation with vitamins E and C on antioxidant enzyme status and histologic changes in hepatic tissue in a rat model of alcoholic liver disease. Methods: This 8-week, blinded, controlled study was conducted at the Department of Internal Medicine, Trakya University, Edirne, Turkey. Weanling albino female protein-deficient Wistar rats weighing similar to 200 g were randomly assigned to I of 6 groups: (1) liquid diet + ethanol + vitamin E 15 mg/kg PO (LDetvitE); (2) liquid diet + ethanol + vitamin C 10 mg/kg PO (LDetvitC); (3) liquid diet + ethanol + vitamin E 15 mg/kg + vitamin C 10 mg/kg PO (LDetvitEC); (4) liquid diet + ethanol (LDet); (5) liquid diet + isocaloric sucrose (LDS); and (6) normal diet (control). The primary end point of the study was to determine whether antioxidant vitamin E/C combination therapy prevents development of hepatic fibrosis (ie, cirrhosis in a period of 1 year). After being euthanized at week 8, the rats were weighed, and their livers and spleens were weighed. Hepatic tissue specimens were histopathologically assessed according to the Brunt system. Hepatic tissue glutathione peroxidase, superoxide dismutase, and catalase activities were determined. Biochemical tissue collagen concentrations were measured to determine the presence of hepatic fibrosis. Results: Seventy-two rats were included in the study (mean [SE] weight, 205 [21] g) (12 rats per group). Initially planned to last 48 weeks, the study was terminated at 8 weeks due to the death of 3 rats in each group (except the LDS group and control group). The relative liver weight was significantly lower in the LDetvitEC group compared with that in the LDet group (mean [SE], 3.7% [0.5%] vs 4.8% [0.9%]; P < 0.01). Mean (SE) hepatic tissue glutathione peroxidase activity was significantly reduced in the LDet-treated rats compared with controls (1.2 [0.2] vs 2.6 [0.3] U/mg protein; P < 0.001). The groups that received supplementation with vitamin E, vitamin C, and vitamins E and C combined had significantly more hepatic glutathione peroxidase activity (mean [SE], 2.1 [0.5], 2.5 [0.2], and 2.6 [0.7] U/mg protein, respectively) compared with the LDet group (1.2 [0.2] U/mg protein) (all, P < 0.001). No significant between-group differences in hepatic superoxide dismutase or catalase activities were found. Compared with controls (14.5 [1.9] mu g collagen/mg protein), the mean (SE) histologic hepatic collagen concentration was significantly higher in all groups (19.2 [1.2], 19.5 [3.3], 18.5 [3.0], 25.9 [3.3], and 21.6 [1.5] mu g collagen/mg protein in the LDetvitE, LDetvitC, LDetvitEC, LDet, and LDS groups, respectively; P < 0.01, P < 0.01, P < 0.05, P < 0.001, and P < 0.001, respectively). Compared with the LDet group, the mean hepatic collagen concentration was significantly lower in the LDetvitE, LDetvitC, and LDetvitEC groups (P < 0.01, P < 0.05, and P < 0.01, respectively). The LDetvitEC group had a significantly lower mean (SE) hepatic inflammatory score compared with the LDet group (0.8 [0.1] vs 1.3 [0.2]; P < 0.05). The LDetvitEC group had a significantly lower mean (SE) hepatic necrosis score compared with that in the LDet group (1.5 [0.2] vs 2.4 [0.3]; P < 0.05). Conclusions: The results of this study in protein-deficient rats fed with a high-fat liquid diet suggest that supplementation with vitamin E, vitamin C, and a combination of vitamins E and C was associated with decreased ethanol-induced hepatic glutathione peroxidase activity and hepatic fibrosis, and that supplementation with vitamins E and C might have attenuated the development of hepatomegaly and hepatic necroinflammation, whereas this result was not found in the group given a liquid diet and ethanol in this 8-week study.