Antioxidants vitamin E and C attenuate hepatic fibrosis in biliary-obstructed rats.
OBJECTIVE
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 mug 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).


CONCLUSIONS
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.
Soylu
Ali-Riza
AR
Division of Gatroenterology, Trakya University, Turkey. alrsoylu@yahoo.com
Aydogdu
Nurettin
N
Basaran
Umit-Nusret
UN
Altaner
Semsi
S
Tarcin
Orhan
O
Gedik
Nursal
N
Umit
Hasan
H
Tezel
Ahmet
A
Dokmeci
Gulbin
G
Baloglu
Huseyin
H
Ture
Mevlut
M
Kutlu
Kemal
K
Kaymak
Kadir
K
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D002779:Cholestasis / Q000150:complications*; D003094:Collagen / Q000378:metabolism; D004357:Drug Synergism; D005260:Female; D006820:Hyaluronic Acid / Q000097:blood; D008026:Ligation; D008103:Liver Cirrhosis / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control*; D008105:Liver Cirrhosis, Biliary / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D018384:Oxidative Stress / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014810:Vitamin E / Q000494:pharmacology*
D000975:Antioxidants; D014810:Vitamin E; D006820:Hyaluronic Acid; D003094:Collagen; D001205:Ascorbic Acid