Combination of Iron Overload Plus Ethanol and Ischemia Alone Give Rise to the Same Endogenous Free Iron Pool |
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Authors: | Odile?Sergent Aldo?Tomasi Daniela?Ceccarelli Alberto?Masini Hans?Nohl Pierre?Cillard Josiane?Cillard Yuri?A?Vladimirov Email author" target="_blank">Andrey?V?KozlovEmail author |
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Institution: | (1) Laboratoire de Biologie Cellulaire et Vegetale, UPRES 3891, UFR des Sciences Pharmaceutiques et Biologiques, University of Rennes 1, 2 AVE du Pr. Léon Bernard, CS, 34317 35043 Rennes Cedex, France;(2) Biomedical Science Department, University of Modena, Via Campi, 287, 41100 Modena, Italy;(3) Research Institute for Biochemical Pharmacology and Toxicology, Veterinary University of Vienna, Veterinaerplatz 1, A-1210 Vienna, Austria;(4) Department of Biophysics, Russian State Medical University, Ostrovitjanova Str. 1, 117997 Moscow, Russia;(5) Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Donaueschinger Str. 13, A-1200 Vienna, Austria |
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Abstract: | Iron overload aggravates tissue damage caused by ischemia and ethanol intoxication. The underlying mechanisms of this phenomenon
are not yet clear. To clarify these mechanisms we followed free iron (“loosely” bound redox-active iron) concentration in
livers from rats subjected to experimental iron overload, acute ethanol intoxication, and ex vivo warm ischemia. The levels of free iron in non-homogenized liver tissues, liver homogenates, and hepatocyte cultures were
analyzed by means of EPR spectroscopy. Ischemia gradually increased the levels of endogenous free iron in liver tissues and
in liver homogenates. The increase was accompanied by the accumulation of lipid peroxidation products. Iron overload alone,
known to increase significantly the total tissue iron, did not affect either free iron levels or lipid peroxidation. Homogenization
of iron-loaded livers, however, resulted in the release of a significant portion of free iron from endogenous depositories.
Acute ethanol intoxication increased free iron levels in liver tissue and diminished the portion of free iron releasing during
homogenization. Similarly to liver tissue, the primary hepatocyte culture loaded with iron in vitro released significantly more free iron during homogenization compared to non iron-loaded hepatocyte culture. Analyzing three
possible sources of free iron release under these experimental conditions in liver cells, namely ferritin, intracellular transferrin-receptor
complex and heme oxygenase, we suggest that redox active free iron is released from ferritin under ischemic conditions whereas
ethanol and homogenization facilitate the release of iron from endosomes containing transferrin-receptor complexes. |
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Keywords: | iron ischemia iron overload ethanol electron paramagnetic resonance |
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