Lysosomal disruption in the pathogenesis of hepatic damage in primary and secondary haemochromatosis.
Ciba Found Symp
317 - 329.
The disruption of lysosomes with release of their content of lytic enzymes was an early concept for the possible role of these organelles in the pathogenesis of tissue damage. Many examples are known of primary lysosomal storage diseases due to a congenital deficiency of certain acid hydrolases. It is suggested that iron overload due to either primary haemochromatosis or transfusional siderosis is a form of acquired secondary lysosomal storage disease. Subcellular fractionation experiments and electron microscopic studies have shown that liver tissue from patients with iron overload has iron-laden lysosomes. Similar results have been found in iron-overloaded rats. In patients, but not in experimental animals, enzymic analyses have shown increased activities of acid hydrolases and strikingly enhanced lysosomal fragility in liver homogenates. When it has been possible to deplete the patients of the excessive iron, these parameters have returned to normal. The possible mechanisms by which the iron compounds disrupt lysosomes, including distension with ferritin or haemosiderin or free-radical-mediated membrane damage, will be discussed.
|Title:||Lysosomal disruption in the pathogenesis of hepatic damage in primary and secondary haemochromatosis.|
|Keywords:||Acetylglucosaminidase, Acid Phosphatase, Bloodletting, Hemochromatosis, Humans, Iron, Liver, Lysosomes|
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