Effects of vitamin E deficiency on hepatic mitochondrial lipid peroxidation and oxidative metabolism in rats with chronic dietary iron overload.

Abstract

Peroxidative decomposition of organelle membrane phospholipids with subsequent organelle dysfunction is a postulated mechanism of liver cell injury in parenchymal iron overload. We studied the effects of different alpha-tocopherol concentrations on hepatic mitochondrial lipid peroxidation and oxidative metabolism in rats with chronic dietary iron overload. There was no evidence of mitochondrial lipid peroxidation (conjugated dienes) or alteration in mitochondrial oxidative metabolism in alpha-tocopherol-deficient rats with normal hepatic iron levels. Significant reductions in mitochondrial respiratory control ratios and oxidative phosphorylation ratios were seen in association with increased conjugated dienes in all three groups of iron-loaded rats regardless of the alpha-tocopherol status (deficient, normal or excess); thus, the alpha-tocopherol deficiency associated with dietary iron overload in this experimental model is not responsible for the mitochondrial abnormalities observed. In addition, chronic parenteral administration of alpha-tocopherol to iron-loaded animals, which increased hepatic levels of this substance 3-fold, did not ameliorate the hepatic mitochondrial lipid peroxidation or the defects in mitochondrial oxidative metabolism resulting from iron overload.