Effects of Iron and Copper Overload on the Human Liver: An Ultrastructural Study

Abstract

Iron and copper ions play important roles in many physiological functions of our body, even though the exact mechanisms regulating their absorption, distribution and excretion are not fully understood. Metal-related human pathology may be observed in two different clinical settings: deficiency or overload. The overload in liver cells of both trace elements leads to multiple cellular lesions. Here we report the main pathological changes observed at transmission electron microscopy in the liver of subjects affected by Beta-thalassemia and by Wilson's disease. The hepatic iron overload in beta-thalassemia patients is associated with haemosiderin storage both in Kupffer cells and in the cytoplasm of hepatocytes. Haemosiderin granules are grouped inside voluminous lysosomes, also called siderosomes. Other ultrastructural changes are fat droplets, proliferation of the smooth endoplasmic reticulum and fibrosis. Apoptosis of hepatocytes and infiltration of sinusoids by polymorphonucleates is also detected in beta-thalassemia. Ultrastructural changes in liver biopsies from Wilson's disease patients are characterized by severe mitochondrial changes, associated with an increased number of perossisomes, cytoplasmic lipid droplets and the presence of lipolysosomes, characteristic cytoplasmic bodies formed by lipid vacuoles surrounded by electron-dense lysosomes. In patients affected by Wilson's disease, nuclei are frequently involved, with disorganization of the nucleoplasm and with glycogen inclusions. On the contrary, no significant changes are detected in Kupffer cells. Our data show that iron and copper, even though are both transition metals, are responsible of different pathological changes at ultrastructural level. In particular, copper overload is associated with mitochondrial damage, whereas iron overload only rarely may cause severe mitochondrial changes. These differences underlay the need for further studies in which biochemical analyses should be associated with ultrastructural data, in order to better understand the molecular ways associated with iron- and copper-related pathology at subcellular level.

Chronic hepatitis without hepatic steatosis caused by citrin deficiency in a child

“…A previous study reported the use of electron microscopy to demonstrate the presence of a large number of lipid droplets in the hepatocytes of an adult with CTLN2; however, this group evaluated an autopsied specimen . The presence of lipid droplets in hepatocytes, as demonstrated by electron microscopy, is not specific to citrin deficiency; however, this finding may be a clue for the diagnosis of citrin deficiency in the absence of fatty changes, as determined by light microscopy. Small vacuoles were observed within the hepatocytes in this patient.…”

Structural basis for promotion of duodenal iron absorption by enteric ferric reductase with ascorbate

“…Despite this long-standing medical use of iron, iron deficiency continues to affect 30% of the world population, is the most severe and widespread nutritional deficiency disorder, and remains the only nutritional deficiency disorder in industrialized countries 4,5 . On the other hand, iron overload causes accumulation of iron in various tissues and can result in cirrhosis 6 , neurodegenerative and cardiovascular diseases (cardiomyopathy, etc.) 7,8 that result from formation of reactive oxygen species through Fenton or Haber−Weiss reactions 9 .…”

Metal Ions Introduced to Proteins by Supramolecular Ligands

“…They form a variety of compounds with interesting spectroscopic and magnetic properties whose practical applications are the subject of ongoing research [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. In the cell, metals are usually found in their complexed form, either as standalone ions or inside specific planar carrier compounds encapsulated by proteins -e.g.…”