RELATIONSHIP BETWEEN FREE IRON LEVEL AND RAT-LIVER MITOCHONDRIAL DYSFUNCTION IN EXPERIMENTAL DIETARY IRON OVERLOAD

The concentration of total iron in the hepatic tissue and mitochondria from rats fed a 2.5% carbonyl iron supplemented diet progressively in creased up to 40 days, then reached nearly a steady-state. By contrast the level of free iron (desferrioxamine-chelatable) exhibited a trans ient but significant increase at 40 days of treatment, only in this pe riod of treatment the induction of lipid peroxidation and the resultin g mitochondrial abnormalities in calcium transport was observed too. T he enhancement of the energy dissipating mitochondrial calcium cycling was found to be associated with a significant decrease of endogenous mitochondrial ATP content. As to the pathophysiological mechanism for hepatocellular injury in iron overload, these results indicated that t he transit pool of free iron may play a critical role in initiating or ganelle dysfunctions, at least in this experimental model of iron over load. (C) 1995 Academic Press, Inc.