Uncoupling and oxidative stress in liver mitochondria isolated from rats with acute iron overload

Abstract

One hypothesis for the etiology of cell damage arising from iron overload is that its excess selectively affects mitochondria. Here we tested the effects of acute iron overload on liver mitochondria isolated from rats subjected to a single dose of i.p. 500 mg/kg iron–dextran. The treatment increased the levels of iron in mitochondria (from 21 ± 4 to 130 ± 7 nmol/mg protein) and caused both lipid peroxidation and glutathione oxidation. The mitochondria of iron-treated rats showed lower respiratory control ratio in association with higher resting respiration. The mitochondrial uncoupling elicited by iron-treatment did not affect the phosphorylation efficiency or the ATP levels, suggesting that uncoupling is a mitochondrial protective mechanism against acute iron overload. Therefore, the reactive oxygen species (ROS)/H+ leak couple, functioning as a mitochondrial redox homeostatic mechanism could play a protective role in the acutely iron-loaded mitochondria.

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Acknowledgments

This work was partially supported by FAPESP, Brasil and by a postgraduate fellowship from the “Red de Macrouniversidades de América Latina y el Caribe”. It is devoted to the memory of Dr. Rizette Ávila González.

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Correspondence to G. L. Pardo Andreu.

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Pardo Andreu, G.L., Inada, N.M., Vercesi, A.E. et al. Uncoupling and oxidative stress in liver mitochondria isolated from rats with acute iron overload. Arch Toxicol 83, 47 (2009). https://doi.org/10.1007/s00204-008-0322-x

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Keywords

  • Iron overload
  • Mitochondria
  • Oxidative stress
  • Reactive oxygen species (ROS)
  • Uncoupling