Hepatic mitochondrial malondialdehyde metabolism in rats with chronic iron overload

✍ Scribed by Robert S. Britton; Rosemary O'Neill; Bruce R. Bacon

• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: English
• Weight: 614 KB
• Volume: 11
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840110116

✦ Synopsis

Peroxidative decomposition of mitochondrial membrane phospholipids with subsequent mitochondrial dysfunction 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. (HEPATOLOGY 1990;11:93-97.) Chronic hepatic iron overload in humans is associated with hepatocellular damage and fibrosis, leading ultimately to cirrhosis (1-4). Although the toxicity of excess iron has been well established clinically (5-11), the specific cytopathological mechanisms whereby hepatocytes are injured in chronic iron overload remain to be fully elucidated (12,13). A proposed mechanism whereby chronic iron overload causes