THE ROLE OF DESFERRIOXAMINE CHELATABLE IRON IN RAT-LIVER MITOCHONDRIAL DYSFUNCTION IN CHRONIC DIETARY IRON OVERLOAD

Lipid peroxidation and organelle dysfunction are important factors in hepatic iron toxicity. The form of the intracellular iron responsible for these abnormalities is still unknown. In order to investigate the iron species inducing cell injury, the level of chelatable iron in the liver mitochondria isolated from rats fed a 2.5% carbonyl iron diet f or 12 weeks was measured by EPR spectroscopy. The presence of lipid pe roxidation products and the energy transducing capability of the mitoc hondrial inner membrane was evaluated in parallel. The total iron conc entration in the liver mitochondria from iron fed rats progressively i ncreased up to 6 weeks, almost reaching a steady-state. By contrast th e level of chelatable iron in mitochondrial fraction transiently incre ased at about 3-6 weeks of treatment. The induction of lipid peroxidat ion and a large decrease of ATP occurred at the same time. The enhance ment of the energy dissipating calcium cycling was in parallel reveale d by studying the mitochondria membrane potential. These results gave experimental evidence to the proposal that the chelatable iron level p lays a critical role in initiating organelle dysfunction, at least in this experimental model. (C) 1997 Elsevier Science S.A.