Cast iron therapy for overload
Iron overload can cause damage in various organs including the liver and endocrine glands. Researchers from the Université de Rennes 1, as part of the project NUTRIENT IRON TOXICITY, aimed to elucidate the links between excess iron in the liver and cell damage in this organ. Cytological studies were performed as well as analyses at the molecular level. Previous research by this particular team of scientists had identified hepcidin as the main hormonal regulator of iron status in the body. Building on this key discovery, the research group went on to investigate the pathogenesis of liver damage by iron overload. First, the scientists found that a surplus of iron in mice caused overexpression of cyclin D1. This protein brings about changes in cell cycle progression and potential tumourigenesis. An increase in liver mass, chromosome set number in hepatocytes and number of cell divisions accompanied the increased protein expression. The other line of investigation centred on two main groups of patients with liver malfunction. Individuals with either untreated hereditary haemochromatosis or alcoholic cirrhosis were tested for abnormal forms of iron. Both groups had detectable levels of labile plasma iron and non-transferrin bound iron (NTBI) where there was a situation of transferrin saturation. The researchers then turned their attention to the development of chelating agents that inhibit the excess absorption of iron and scavenge NTBI. Two alternatives to the chelator CP20, known as Ferriprox® were tested. Both O-trensox and CP411 were shown to be more effective than CP20 for inhibition of tumour cell proliferation and protection from iron-related hepatocyte toxicity. Molecular data from this research can lead to the identification of genetic and biochemical markers, not only for diagnosis but also prognosis, in an iron overload situation. Furthermore, it has extended the boundaries in chelation therapy research for more effective treatments.
