Iron and Copper Toxicity in Rat Liver: A Kinetic and Holistic Overview
Iron and copper are bioelements and vital transition metals whose deficiency or excess
in the organism are associated with pathologic situations.
Both metals are clearly hermetic, they are required at low levels for human health
but at higher levels they produce toxic effects in liver and brain.
The metal toxicity seems due to their participation in the Haber-Weiss
redox reaction that produces the highly reactive HO.
The intracellular steady-state concentrations of reactive
oxygen species indicate that H2 O2 and ROOH are the quantitatively predominant
species by a factor of 104.
Currently, there are two hypotheses for the molecular mechanism of transition metal
toxicity in mammalian organs. The two hypotheses are not incompatible and it is likely that the
two processes occur simultaneously.
The first one considers that the reduced forms Fe2+ and Cu+
catalyze the hemolytic scission of the O-O bond in H2
O2 and ROOH in a Fenton-like reaction
to produce HO• and RO• radicals.
The second one considers the reaction of Fe3+ and Cu2+ with
intracellular reduced glutathione (GSH), due to the high affinity of the two metals ions for the
thiol (-SH) group. This depletes cells of GSH that is equilibrated with essential thiol groups in
enzymes and regulatory factors.
Concerning the first hypothesis, there are two points of view of
the O-O bond hemolysis: a classical one where Fe2+ or Cu+
directly catalyzes the reaction and a second one, in which Fe2+ and Cu+
bind to a specific peptide or protein that reacts with H2 O2
generating HO• , that is able to oxidize neighboring amino acids
and to produce protein crosslinking, fragmentation and denaturation.
Liver Res Open J. 2017; 2(1): 9-13. doi: 10.17140/LROJ-2-110