Iron-induced oxidant stress leads to irreversible mitochondrial dysfunctions and fibrosis in the liver of chronic iron-dosed gerbils. The effect of silybin
A. Masini et al., Iron-induced oxidant stress leads to irreversible mitochondrial dysfunctions and fibrosis in the liver of chronic iron-dosed gerbils. The effect of silybin, J BIOENER B, 32(2), 2000, pp. 175-182
Hepatic iron toxicity because of iron overload seems to be mediated by lipi
d peroxidation of biological membranes and the associated organelle dysfunc
tions. However, the basic mechanisms underlying this process in vivo are st
ill little understood. Gerbils were dosed with weekly injections of iron-de
xtran alone or in combination with sylibin, a well-known antioxidant, by ga
vage for 8 weeks. A strict correlation was found between lipid peroxidation
and the level of desferrioxamine chelatable iron pool. A consequent derang
ement in the mitochondrial energy-transducin capability, resulting from a r
eduction in the respiratory chain enzyme activities, occurred. These irreve
rsible oxidative anomalies brought about a dramatic drop in tissue ATP leve
l, The mitochondrial oxidative derangement was associated with the developm
ent of fibrosis in the hepatic tissue. Silybin administration significantly
reduced both functional anomalies and the fibrotic process by chelating de
sferrioxamine chelatable iron.