Hepatic mitochondrial malondialdehyde metabolism in rats with chronic iron overload

Authors

  • Robert S. Britton,

    1. Departments of Medicine, Case Western Reserve University School of Medicine, Cleveland Metropolitan General Hospital, Cleveland, Ohio 44109, and Louisiana State University School of Medicine, Shreveport, Louisiana 71130
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    • Recipient of a Medical Reserch Council of Canada Fellowship.

  • Rosemary O'Neill,

    1. Departments of Medicine, Case Western Reserve University School of Medicine, Cleveland Metropolitan General Hospital, Cleveland, Ohio 44109, and Louisiana State University School of Medicine, Shreveport, Louisiana 71130
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  • Bruce R. Bacon

    Corresponding author
    1. Departments of Medicine, Case Western Reserve University School of Medicine, Cleveland Metropolitan General Hospital, Cleveland, Ohio 44109, and Louisiana State University School of Medicine, Shreveport, Louisiana 71130
    • Section of Gastroenterology and Hepatology, Louisiana State University School of Medicine, 1501 Kings Highway, Shreveport, Louisiana 71130–3932
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  • This work was presented in part atthe annual meeting of the American Association for the Study of Liver Diseases, Chicago, Illinois, November 1986, and was published in abstract form (HEPATOLOGY 1986;6:1208)

Abstract

Peroxidative decomposition of mitochondrial membrane phospholipids with subsequent mitochondrial dysfunctin is a postulated mechanism of liver cell injury in parenchymal iron overload. Malondialdehyde is formed when polyunsaturated fatty acids of membrane phospholipids undergo peroxidative decomposition, and it is metabolized by aldehyde dehydrogenase. We studied mitochondrial metabolism of malondialdehyde in rats with chronic dietary iron overload. Hepatic malondialdehyde concentrations were significantly increased in iron-loaded livers, and mitochondrial respiratory control ratios using glutamate as a substrate were decreased by 47% largely owing to reductions in state 3 respiration. When exogenous malondialdehyde was added to mitochondrial fractions, there was significantly less metabolism of malondialdehyde in mitochondria of iron-loaded livers as compared with controls. In addition, there was a 28% decrease in mitochondrial aldehyde dehydrogenase in iron-loaded livers but no change in cytosolic aldehyde dehydrogenase. Increased hepatic malondialdehyde in chronic iron overload may result from a combination of increased production and decreased metabolism of malondialdehyde, both of which may be due to ironinduced mitochondrial lipid peroxidation.

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