The effect of vitamin e supplementation on hepatic fibrogenesis in
chronic dietary iron overload.
Brown, Kyle E., John E. Poulos, Lin Li, Assaad M. Soweid, Grant A.
Ramm, Rosemary O'neill, Robert S. Britton, and Bruce R. Bacon.
Division of Gastroenterology and Hepatology, Department of Internal
Medicine, Saint Louis University School of Medicine, St. Louis, MO
63110
APStracts 3:0169G, 1996.
It has been suggested that lipid peroxidation plays an important role
in hepatic fibrogenesis resulting from chronic iron overload. Vitamin
E is an important lipid soluble antioxidant that has been shown to be
decreased in patients with hereditary hemochromatosis and in
experimental iron overload. The aim of this study was to determine
the effects of vitamin E supplementation on hepatic lipid
peroxidation and fibrogenesis in an animal model of chronic iron
overload. Rats were fed the following diets for 4, 8, or 14 mo:
standard chow (control), chow with supplemental vitamin E (200 IU/kg,
control + E), chow with carbonyl iron (Fe), and chow with carbonyl
iron, supplemented with vitamin E (200 IU/kg, Fe + E). Iron loading
resulted in significant decreases in hepatic and plasma vitamin E
levels at all time points which were overcome by vitamin E
supplementation. Thiobarbituric acid-reactive substances (an index of
lipid peroxidation) were increased 3- to 5-fold in the iron-loaded
livers; supplementation with vitamin E reduced these levels by at
least 50% at all time points. Hepatic hydroxyproline levels were
increased 2-fold by iron loading. Vitamin E did not affect
hydroxyproline content at 4 or 8 mo, but caused an 18% reduction at
14 mo in iron-loaded livers. At 8 and 14 mo, vitamin E decreased the
number of a-smooth muscle actin-positive stellate cells in iron
-loaded livers. These results demonstrate a dissociation between lipid
peroxidation and collagen production and suggest that the
profibrogenic action of iron in this model is mediated through
effects which cannot be completely suppressed by vitamin E.
Received 10 January 1996; accepted in final form 23 August 1996.
APS Manuscript Number G11-6.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 September 1996